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The double-blinded randomized trial is considered the gold standard to estimate the average causal effect (ACE). The naive estimator without adjusting any covariate is consistent. However, incorporating the covariates that are strong predictors of the outcome could reduce the issue of unbalanced covariate distribution between the treated and controlled groups and can improve efficiency. Recent work has shown that thanks to randomization, for linear regression, an estimator under risk consistency (e.g. Random Forest) for the regression coefficients could maintain the convergence rate even when a nonparametric model is assumed for the effect of covariates. Also, such an adjusted estimator will always lead to efficiency gain compared to the naive unadjusted estimator. In this paper, we extend this result to the competing risk data setting and show that under similar assumptions, the augmented inverse probability censoring weighting (AIPCW) based adjusted estimator has the same convergence rate and efficiency gain. Extensive simulations were performed to show the efficiency gain in the finite sample setting. To illustrate our proposed method, we apply it to the Women's Health Initiative (WHI) dietary modification trial studying the effect of a low-fat diet on cardiovascular disease (CVD) related mortality among those who have prior CVD. [ABSTRACT FROM AUTHOR]

Strong evidence supports the paramount importance of the composition of the diet for health. Not only diet should provide nutritional adequacy, but some foods and dietary components can also support the management of common chronic diseases, with mechanisms independent of nutritional adequacy. Among the various intervention diets, low-fat vegan diets have been shown to be effective for cardiometabolic health, mainly influencing insulin resistance, adiposity, and blood lipids. This type of diet relies on reducing or eliminating all added fats and choosing low-fat foods, mainly unprocessed whole-plant foods. We hereby propose a tool for planning low-fat vegan diets, the VegPlate Low-Fat (VP_LF), which has been obtained from a specific adaptation of the VegPlate method, which was already presented in previous publications for adults and some life stages and situations. The reduction in fats in the diet, which ranges between 10% and 15% of total energy, and the varied inclusion of foods from plant groups make it easier to provide adequate amounts of all nutrients with a normal- or lower-calorie intake, in comparison with diets that do not limit fat intakes. We expect that this new proposal will help nutrition professionals embrace low-fat diets as a first-line intervention for individuals affected by different health conditions who can benefit from these diets. [ABSTRACT FROM AUTHOR]

Nutritional approach has been intensely investigated in inflammatory bowel disease (IBD) patients, but, despite many sparse reports, at present, there is not a universally accepted specific diet. In fact, nutritional requirements and, therefore, the ideal diet, may vary according to disease type, extension and activity. Among nutritional related issue in IBD, obesity has become a relevant one. In fact, obesity and IBD are both increasing in prevalence in last decades, and more and more IBD patients are overweight or obese. These two conditions present common metabolic pathways, leading to dysbiosis and mucosal barrier dysfunction, but the real clinical relationship and the potential reciprocal relative influences are not clear. In order to control weight, many IBD patients follow different weight loss diets, often without any specialized medical advice. Among those, low carb, intermittent fasting, paleolithic, and low-fat diets are some of the most popular, and plant based and Mediterranean diet, even though they are not just strictly weight loss diets, are followed by many IBD patients even for weight control. All the diets mentioned above have been effectively associated with weight loss, reduction in waist circumference and body mass index. However, there are still conflicting data regarding safety in IBD patients and potential experimental and clinical anti-inflammatory effect. In the present review, we described potential relations between obesity and IBD, and we analysed available evidence on efficacy and safety of weight loss diets in IBD patients, in order to provide a practical guide to physicians. [ABSTRACT FROM AUTHOR]

The Healthy Eating Index 2010 (HEI-2010) and Alternative Healthy Eating Index 2010 (AHEI-2010) are commonly used to measure dietary quality in research settings. Neither index is designed specifically to compare diet quality between low-carbohydrate (LC) and low-fat (LF) diets. It is unknown whether biases exist in making these comparisons. The aim was to determine whether HEI-2010 and AHEI-2010 contain biases when scoring LC and LF diets. Secondary analyses of the Diet Intervention Examining the Factors Interacting With Treatment Success (DIETFITS) weight loss trial were conducted. The trial was conducted in the San Francisco Bay Area of California between January 2013 and May 2016. Three approaches were used to investigate whether biases existed for HEI-2010 and AHEI-2010 when scoring LC and LF diets. DIETFITS participants were assigned to follow healthy LC or healthy LF diets for 12 months (n = 609). Mean diet quality index scores for each diet were measured. Approach 1 examined both diet quality indices' scoring criteria. Approach 2 compared scores garnered by exemplary quality LC and LF menus created by registered dietitian nutritionists. Approach 3 used 2-sided t tests to compare the HEI-2010 and AHEI-2010 scores calculated from 24-hour dietary recalls of DIETFITS trial participants (n = 608). Scoring criteria for both HEI-2010 (100 possible points) and AHEI-2010 (110 possible points) were estimated to favor an LF diet by 10 points. Mean scores for exemplary quality LF menus were higher than for LC menus using both HEI-2010 (91.8 vs 76.8) and AHEI-2010 (71.7 vs 64.4, adjusted to 100 possible points). DIETFITS participants assigned to a healthy LF diet scored significantly higher on HEI and AHEI than those assigned to a healthy LC diet at 3, 6, and 12 months (all, P <.001). Mean baseline scores were lower than mean scores at all follow-up time points regardless of diet assignment or diet quality index used. Commonly used diet quality indices, HEI-2010 and AHEI-2010, showed biases toward LF vs LC diets. However, both indices detected expected changes in diet quality within each diet, with HEI-2010 yielding greater variation in scores. Findings support the use of these indices in measuring diet quality differences within, but not between, LC and LF diets. [ABSTRACT FROM AUTHOR]

The article "Update on Equine Exertional Muscle Disorders" provides a comprehensive overview of various muscle diseases in horses, focusing on exertional rhabdomyolysis (ER) disorders. It discusses the clinical presentations, pathophysiology, diagnosis, and management strategies for different types of muscle disorders in horses, such as PSSM1, PSSM2-ER, RER, MH, MFM-ER, and MFM-WB. The article emphasizes the importance of thorough history-taking, physical examination, genetic testing, and dietary and exercise management in diagnosing and treating these muscle disorders in horses. [Extracted from the article]

Purpose: Pre‐operative eating disorders are well documented within the metabolic and bariatric surgery (MBS) population, yet subthreshold dieting attempts are less understood. The objectives of this study were to define and categorize patients' preoperative dieting attempts, and to determine how attempts are associated with postoperative outcomes, eating disorders, and demographics. Materials and Methods: Three hundred twenty‐one patients (81.0% female; 68.3% White) who had MBS (57.3% Roux‐en‐Y) between 2019 and 2020 were included. Preoperative dieting attempt responses were categorized as provider‐managed, non‐medically managed, and self‐directed attempts; subtypes of dieting methods (e.g., low calorie) were described. Descriptive analyses were conducted for attempt categories and subtypes, and between attempts and readmissions, complications, eating disorders, and demographics. ANOVAs determined associations between attempts and %TWL at 6 and 12 months. Results: Patients reported an average of five to six preoperative dieting attempts; self‐directed attempts were the most common (91.9%), and exercise was the most common subcategory (70.7%). Patients with ≥ 1 provider‐managed attempt were less likely to experience a complication (p < 0.001) and more likely to experience readmission (p = 0.018). Patients with 1 self‐directed attempt were less likely to experience a complication (p = 0.045) and readmission (p < 0.001). Patients who experienced ≥ 2 low fat diet attempts were more likely to have complications (p < 0.001) and readmissions (p = 0.008); patients with ≥ 2 VLCD attempts were more likely to have a complication (p < 0.001). Patients who experienced ≥ 2 non‐medically managed attempts had higher preoperative BMIs (p = 0.03). Discussion: Given that patients engaged in frequent dieting attempts that fall outside formal assessments, future work should seek to expand pre‐operative assessments. [ABSTRACT FROM AUTHOR]

Background: Previous researches on the effect of low-fat diet (LF) on insulin-like growth factor-1 (IGF-1), and its binding proteins (IGFBPs) did not reach a consensus result, and there is no study summarizing these findings. Thus, this systematic review and meta-analysis of randomized control trials (RCTs) was performed to pool available evidence and answer the question whether dietary fat can affect IGF-1 and IGFBPs or not. Methods: PubMed, Scopus, ISI Web of Science, Google, Google scholar, ProQuest, and the Cochrane Library were searched without language restrictions until July 2, 2024 to retrieve related studies. Weighted mean difference and the corresponding variance were considered as the effect size. Standard tools were applied to assess the quality of the studies and evidence. Results: Pooling data of the eligible studies showed no significant effect of LF diet on IGF-1 (six studies; participants = 1029.; pooled mean = 1.63 ng/ml, 95% CI= [-1.34, 4.59], P = 0.28, I2 = 0.00%), and IGFBP-3 (five studies; participants = 969; pooled mean = 65.24 ng/ml, 95% CI= [-169.53, 300.00], P = 0.59, I2 = 0.0%). The results of subgroup analysis for IGF-1 and IGFBP-3 also demonstrated no significant findings. For IGFBP-1, available evidence is insufficient since only two studies have been performed yet and their results are contradictory. Conclusions: This study indicated no significant effect of LF diet on IGF-1, and IGFBP-3 concentrations. Low certainty of evidence indicates that available evidence cannot support to draw a firm conclusion and future researches may change the estimates. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. The ketogenic diet (KD), a diet high in fat and low in carbohydrates, has been applied clinically for the treatment of obese women with PCOS. We have previously demonstrated that KD improved the reproductive phenotype in an androgen-induced PCOS mouse model, yet the underlying molecular mechanisms remain largely unclear. The aim of the present study was to investigate the effect of KD on the reproductive phenotype of a letrozole-induced PCOS mouse model. Methods: Female C57BL/6N mice were divided into three groups, designated control, letrozole, and letrozole + KD groups. Mice of control and letrozole groups were fed the control diet, whereas letrozole + KD mice were fed a KD with 89.9% (kcal) fat for 3 weeks after the PCOS mouse model was generated. β-hydroxybutyrate (BHB), the most abundant ketone body in the body, was used to treat KGN cells with testosterone (T) to simulate the KD effect on PCOS mouse ovaries in vitro. Results: Our data showed that KD treatment significantly increased blood ketone levels and reduced body weight. Ovarian functions were improved in some letrozole + KD mice. Results from in vitro experiments indicated mitochondrial damage owing to high T levels, which resulted in the leakage of cytochrome C and mitochondrial DNA into the cytosol and thus induced the activation of the intracellular caspase cascade and the cGAS-STING-NF-κB pathway, leading to granulosa cell inflammation and apoptosis. BHB exhibited certain protective effects on mitochondria of T-treated KGN cells via inhibiting the cGAS-STING pathway. Moreover, the cGAS-STING pathway was activated in ovaries of letrozole mice and was down-regulated in letrozole + KD mice. Conclusion: These findings, for the first time, revealed that hyperandrogenism induced ovarian dysfunction possibly through activation of the cGAS-STING pathway, which could be partially inhibited by ketone bodies produced from KD administration. [ABSTRACT FROM AUTHOR]

Background: The global burden of non-alcoholic fatty liver disease (NAFLD) has significantly risen over the past decade. Dietary intake strongly influences its development and should be a component of any prevention and treatment plan strategy. Dietary pattern analysis enables the investigation of the overall diet and permits the consideration of interactions and cumulative effects of dietary components. The current study aimed to systematically review observational studies and intervention trials to determine the associations between various dietary patterns and NAFLD. Methods: The protocol was written according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed, Embase, and the Cochrane Library. We included studies that reported a priori dietary pattern (i.e., diet quality scores) or a posteriori method, which identified existing eating patterns (i.e., principal component analysis) in adult participants. Two investigators conducted independent screening, extraction, and quality assessment using the Newcastle‒Ottawa or Jadad scale. A third reviewer resolved conflicts. Results: We identified 27 relevant observational and 16 interventional studies from 16 countries. A Mediterranean or DASH diet might prevent and improve NAFLD, whereas dietary patterns such as Western dietary patterns characterized by high consumption of sweets and animal foods such as red meat and fast food are positively associated with NAFLD. A low-carbohydrate diet effectively prevents and treats NAFLD; however, we need more research on the effects of a low-fat diet and the type of fats. Conclusion: Healthy dietary patterns, mainly plant-based or adjusted macronutrient distributions, such as the adoption of a low-carbohydrate diet, are linked to a reduced risk of NAFLD and could halt its progression. We proposed recommendations for future studies to fill the gap in knowledge regarding the management of NAFLD via dietary modifications. [ABSTRACT FROM AUTHOR]

Background: A low-fat vegan diet, supplemented with soybeans, has been shown effective in reducing postmenopausal hot flashes. This secondary analysis assessed the association of a plant-based index (PDI), healthful (hPDI), and unhealthful (uPDI), with changes in hot flashes in postmenopausal women. Methods: Participants (n = 84) were randomly assigned to a low-fat vegan diet supplemented with soybeans (n = 42) or a control group (n = 42) for 12 weeks. Three-day dietary records were analyzed and PDI indices were calculated. A repeated measures analysis of variance (ANOVA) was used for statistical analysis. Results: All three scores increased in the vegan group, compared with no change in the control group; the effect sizes were: PDI + 9.8 (95% CI + 5.8 to + 13.8; p < 0.001); hPDI + 10.9 (95% CI + 6.4 to + 15.3; p < 0.001); and uPDI + 3.6 (95% CI + 0.5 to + 6.6; p = 0.02). The change in all three scores negatively correlated with change in body weight (PDI: r=-0.48; p < 0.001; hPDI: r=-0.38; p = 0.002; and uPDI: r=-0.31; p = 0.01). The changes in PDI and uPDI were negatively associated with changes in severe hot flashes (r=-0.34; p = 0.009; and r=-0.43; p < 0.001, respectively), and associations remained significant after adjustment for changes in body mass index (r=-0.31; p = 0.02; and r=-0.41; p = 0.001, respectively). Conclusions: These findings suggest that minimizing the consumption of animal products and oil may be an effective strategy to reduce hot flashes in postmenopausal women, and that categorization of plant foods as "healthful" or "unhealthful" may be unwarranted. Trial registration: ClinicalTrials.gov, NCT04587154, registered on Oct 14, 2020. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) play crucial roles in regulating inflammation and cellular senescence. Among them, miR-146a has emerged as a key modulator of inflammation, but its role in obesity-induced senescence remains unexplored. This study investigates the involvement of miR-146a in high-fat diet (HFD)-induced hypothalamic senescence and in protective effects of elocalcitol (Elo), a non-hypercalcemic, fluorinated vitamin D analog on HFD-induced senescence. Results: Wild-type (WT) HFD-fed mice exhibited increased body weight, impaired locomotor activity, and cognitive decline compared to low-fat diet (LFD) controls. In the brain, HFD induced senescence markers (p16, p21), β-galactosidase activity (β-gal) of microglia, and increased expression of senescence associated secretory phenotype (SASP) cytokines (Il1b, Il18, Tnf, Il6) in activated hypothalamic microglia. In the liver, increased p21 and SASP cytokines were detected, although p16 and β-gal levels remained unchanged. Importantly, miR-146a expression was significantly downregulated in the hypothalamus following HFD exposure in WT mice, while miR-146a knockout (Mir146a-/-) mice subjected to HFD showed augmented hypothalamic senescence characterized by higher levels of p16, p21, and β-gal + microglial cells as compared to WT mice. The SASP profile remained similar between Mir146a-/- HFD and WT HFD mice. Among miR-146a target genes, smad4 was upregulated the hypothalamus of HFD-fed mice, with a more pronounced increase in the hypothalamus of HFD-fed Mir146a-/- mice. Further, treatment with Elo upregulated miR-146a expression in both the hypothalamus and the liver, lowered body weight and improved cognitive function, while reducing senescence markers and SASP cytokines in WT HFD mice. These effects were absent in Mir146a-/- HFD mice when treated with Elo, indicating the dependence of Elo's therapeutic efficacy on miR-146a. Conclusion: Elocalcitol prevents development of senescence in microglia via modulation of miR-146a expression, while miR-146a provides protection against HFD-induced cellular senescence in the hypothalamus most probably via inhibition of TGF/Smad4 pathway. These findings highlight Elo and miR-146a as promising therapeutic candidates for ameliorating obesity-related neuroinflammation and senescence. [ABSTRACT FROM AUTHOR]

The experiment aimed to investigate the effects of pomelo fruit polysaccharide on reducing fat deposition and improving liver health in Epinephelus coioides. Selected Epinephelus coioides with a body weight of about 11 g, divided into five groups. There were three replicates in each group: Control group (fat content 11.06%), low-fat group (fat content 7.49%), low-fat + pomelo fruit polysaccharide group (low-fat diet +400 mg/kg pomelo fruit polysaccharide), high-fat group (fat content 15.32%) and high-fat + pomelo fruit polysaccharide group (high-fat diet +400 mg/kg pomelo fruit polysaccharide). 20 fish per repeat. The pre-test period was two weeks, the formal test period was eight weeks. The results showed that the weight gain rate (WGR) and specific growth rate (SGR) of Epinephelus coioides in the low-fat group were significantly lower than those in the control group (P<0.05). The low-fat + pomelo fruit polysaccharide group and the high-fat + pomelo fruit polysaccharide group were higher than the low-fat group and the high-fat group, respectively, but without significant differences (P>0.05). Compared to the high-fat group, the whole fish and muscle crude fat content and hepatosomatic index (HSI) in the high-fat + pomelo fruit polysaccharide group were significantly reduced (P<0.05). The low-fat group and high-fat group showed liver damage, but the low-fat + pomelo fruit polysaccharide group and the high-fat + pomelo fruit polysaccharide group exhibited significant improvements in liver tissue structure damage, and the liver lipid droplet content in the high-fat + pomelo fruit polysaccharide group was significantly lower than that in the high-fat group. The high-fat + pomelo fruit polysaccharide group significantly inhibited the upregulation of inflammation and apoptosis-related genes interleukin-1β (IL-1β), interleukin-8 (IL-8), caspase protease-3 (caspase-3), and caspase protease-8 (caspase-8). The study indicates that the addition of pomelo polysaccharide in low fat and high fat diets had no effect on the growth performance of Epinephelus coioides, but it could reduce the increase of crude fat content in whole fish and muscle and fat deposition in liver caused by high fat diet, enhance immune function and improve liver health. [ABSTRACT FROM AUTHOR]

Background/Objectives: Emerging data support evidence of the essential role of glucagon for lipid metabolism. However, data on the role of dietary fat intake for glucagon secretion is limited. This analysis investigated whether altering nutritional fat intake affects glucagon levels in healthy subjects. Methods: A total of 92 twins (age: 31 ± 14 years, BMI: 23 ± 3 kg/m2) consumed two 6-week diets: first a low-fat, high-carbohydrate diet (LFD) followed by an isocaloric high-fat, low-carbohydrate diet (HFD). In total, 24 twins (age: 39 ± 15 years, BMI: 24 ± 2 kg/m2) continued with a high-protein diet (HPD). Clinical investigations were performed after 6 weeks of the LFD, after 1 and 6 weeks of the HFD and after 6 weeks of the HPD. Results: The LFD caused a significant decrease in fasting glucagon (−27%, p < 0.001) compared to baseline. After 6 weeks of the HFD, glucagon increased (117%, p < 0.001 vs. LFD), while free fatty acids decreased. Six weeks of the HPD further increased glucagon levels (72%, p = 0.502 vs. HFD), although fasting amino acid levels remained constant. Fasting insulin and HOMA-IR moderately increased after one week of the HFD, while six weeks of the HPD significantly decreased both. The fasting glucagon-to-insulin ratio decreased during the LFD (p < 0.001) but increased after the HFD (p < 0.001) and even further increased after the HPD (p = 0.018). Liver fat, triglycerides and blood glucose did not increase during the HFD. The heritability of glucagon levels was 45% with the LFD. Conclusions: An HFD increases glucagon levels and the glucagon-to-insulin ratio under isocaloric conditions compared to an LFD in healthy lean subjects. This rise in glucagon may represent a metabolic response to prevent hepatic steatosis, as glucagon increases have been previously shown to induce hepatic fat oxidation. [ABSTRACT FROM AUTHOR]

Purpose: This study used an animal model to examine the effects of environmental enrichment (EE) and caloric restriction (CR) on hippocampal changes in early adulthood in a rat model. Methods: Male Sprague-Dawley rats were randomly assigned to control, EE, and CR groups. After 8 weeks of EE and CR, behavioral, biochemical, and molecular biological assessments were performed. Behavioral tests included the open field test for anxiety-like behavior, the eight-arm radial maze test for spatial learning, and the passive avoidance test for short-term memory. Glucose tolerance was assessed with an intraperitoneal glucose tolerance test, and the molecular markers associated with neuroinflammation were evaluated. Results: Both EE and CR reduced anxiety-like behaviors, as evidenced by increased time in the central region of the open field test and decreased rearing. However, neither EE nor CR significantly improved short-term memory or spatial learning. Nonetheless, the CR group showed a decrease in eight-arm radial maze completion time, indicating potential for enhanced learning. Both interventions improved glucose tolerance, with lower fasting blood glucose levels in the CR and EE groups. Molecular biological analyses showed that neuroinflammatory markers interleukin-6 and inducible nitric oxide synthase were reduced in the EE and CR groups and that Iba-1 had anti-inflammatory effects due to its neuroprotective action. Conclusion: EE and CR were beneficial for emotional and metabolic health in early adult rats due to reductions in anxiety-like behaviors and neuroinflammation with a concomitant improvement in glucose metabolism. However, the effects of these modalities on improving cognitive function were limited, illustrating the need for further research. [ABSTRACT FROM AUTHOR]

Hypertriglyceridemia is an important and well documented adverse effect caused by the immunosuppressive agent sirolimus. Patients treated with sirolimus require frequent monitoring of blood lipid panels and prompt treatment with appropriate triglyceride-lowering therapies. We report the case of an asymptomatic 65-year-old female stem cell transplant recipient who developed extreme hypertriglyceridemia with levels > 19,000 mg/dL (214 mmol/L) (reference range, < 150 mg/dL [< 1.7 mmol/L]), secondary to sirolimus for prophylaxis of graft-vs-host disease. Acute treatment included admission to the intensive care unit for initiation of an intravenous insulin infusion, low-fat diet, and discontinuation of sirolimus. These measures, in addition to initiation of oral triglyceride-lowering agents and improved glycemic control, led to substantial improvement in triglyceride levels. [ABSTRACT FROM AUTHOR]

Time-restricted feeding (TRF) has emerged as a promising dietary approach for improving metabolic parameters associated with obesity. However, it remains largely unclear whether TRF offers benefits for obesity related to exposure to light at night. This study examined whether lean and obese mice under chronic light exposure could benefit from TRF intervention. Six-week-old C57BL/6 male mice were fed either a low-fat diet or a high-fat diet under a 12 h light/12 h dark cycle for 6 weeks. They were then divided into three subgroups: control light, chronic 24 h light, and chronic light with a daily 10 h TRF. Chronic light exposure led to increased weight gain and higher expression of inflammatory and fibrotic markers in the adipose tissue of both lean and obese mice. It also increased hepatic triglyceride content in mice, regardless of their weight status. TRF protected both lean and obese mice from weight gain, normalized inflammatory and fibrotic gene expression, and reduced adipose tissue collagen and liver triglyceride accumulation caused by light exposure alone or in combination with obesity. These results suggest that TRF could have clinical implications for preventing obesity associated with night shift work, regardless of current weight status. [ABSTRACT FROM AUTHOR]

The US dietary supplement (DS) market has expanded exponentially since 1994, with an estimated 50,000–80,000 individual products currently available. Many DS claim cholesterol or cardiovascular benefits. Overall, well-designed randomized controlled trials (RCTs) with DS are lacking, while studies with favorable results are commonly performed outside of the USA, resulting in inconsistent findings. The expansion of the DS market has limited the ability of the Food and Drug Administration to regulate and prevent substandard products. Eicosapentaenoic acid and docosahexaenoic acid are components of DS fish oil. Recent RCTs utilizing prescription fish oil have provided mixed findings and small but significant safety concerns. Hence, the role of DS fish oil is limited and no longer recommended by major cardiovascular guidelines. Concerns have also been observed from RCTs utilizing prescription niacin, resulting in a negligible role for DS niacin in lipid management. Red yeast rice has demonstrated significant low-density lipoprotein cholesterol (LDL-C) reductions in studies performed worldwide, including the USA. However, quality concerns and inconsistent study results have been reported on multiple occasions. Other common DS have produced modest reductions in LDL-C and may provide other cardiometabolic benefits, including garlic, phytosterols, psyllium, and berberine. Yet inconsistent study results and quality concerns continue to be reported for most. Nonetheless, there is a need for alternative therapies that can safely and effectively reduce cardiovascular risk. However, until DS routinely match label claims and are free of contaminants, the agents have a limited role in clinical practice. [ABSTRACT FROM AUTHOR]

In the Women's Health Initiative Dietary Modification randomized trial, the dietary intervention reduced breast cancer mortality by 21% (P =.02) and increased physical activity as well. Therefore, the aim was to examine whether or not these lifestyle changes attenuated age-related physical functioning decline. In a randomized trial, the influence of 8 years of a low-fat dietary pattern intervention was examined through 20 years of cumulative follow-up. From 1993 to 1998, 48,835 postmenopausal women, ages 50 to 79 years with no prior breast cancer and negative baseline mammogram were randomized at 40 US clinical centers to dietary intervention or usual diet comparison groups (40 out of 60). The intervention significantly reduced fat intake and increased vegetable, fruit, and grain intake. In post hoc analyses, physical functioning, assessed using the RAND 36-Item Short Form Health Survey, evaluated quality or limitations of 10 hierarchical physical activities. Longitudinal physical functioning, reported against a disability threshold (when assistance in daily activities is required) was the primary study outcome. Semiparametric linear mixed effect models were used to contrast physical functioning trajectories by randomization groups. Physical functioning score, assessed 495,317 times with 11.0 (median) assessments per participant, was significantly higher in the intervention vs comparison groups through 12 years of cumulative follow-up (P =.001), representing a reduction in age-related functional decline. The intervention effect subsequently attenuated and did not delay time to the disability threshold. Among women in the dietary intervention vs comparison groups, aged 50 to 59 years, who were physically inactive at entry, a persistent, statistically significant, favorable influence on physical functioning with associated delay in crossing the disability threshold by approximately a year was seen (P value for interaction =.007). In the Women's Health Initiative Dietary Modification randomized trial, a dietary intervention that significantly reduced breast cancer mortality also significantly reduced age-related functional decline through 12 years, which was attenuated with longer follow-up. [ABSTRACT FROM AUTHOR]

The Women's Health Initiative (WHI) has been a major contributor to diet and chronic disease research among postmenopausal US women over its 30+ year history (1993 to present). The WHI program included full-scale randomized trials of a low-fat dietary pattern high in fruits, vegetables, and grains, and of calcium and vitamin D supplementation, each with designated primary and secondary chronic disease outcomes. The history of these trials will be briefly reviewed here, along with principal findings that included evidence for breast cancer-related benefits for each of the 2 interventions. In recent years, WHI investigators have developed an active research program in nutritional biomarker development and in the application of these biomarkers in WHI cohorts, among various other nutritional epidemiology uses of WHI observational study resources. The intake biomarker work, which primarily relies on blood and urine metabolomics profiles, lends support to the low-fat dietary pattern trial results, and supports chronic disease benefits of higher carbohydrate diets more generally, especially through the fiber component of carbohydrate. [ABSTRACT FROM AUTHOR]

Epidemiological studies demonstrate that maternal obesity and maternal allergy are major risk factors for asthma in offspring. However, the impact of maternal allergy and obesity on offspring lung insulin signaling and allergen responsiveness is not known. To evaluate this, allergic and nonallergic female mice were fed a high-fat diet or low-fat diet from 7 wk before pregnancy until weaning. Neonatal pups were allergen-sensitized and allergen-challenged and then were assessed for obesity, insulin signaling, and allergic inflammation. Compared with pups of nonobese nonallergic mothers, allergen-challenged pups of obese nonallergic mothers, nonobese allergic mothers, and obese allergic mothers had bronchoalveolar lavage (BAL) eosinophilia, with the pups of obese allergic mothers having the highest BAL eosinophilia. These pups also had lower insulin-induced lung AKT phosphorylation, indicating a decrease in lung parenchymal insulin sensitivity. In cross-fostering experiments, allergen-challenged pups exposed to both pre- and postnatal obese allergic mothers had the highest level of BAL eosinophilia. Maternal obesity or allergy increased offspring serum allergen-specific IgE and interleukin-5 that was highest when the mother was both obese and allergic. Also, allergen-challenged pups exposed to both pre- and postnatal obese allergic mothers had the highest level of interleukin-5. In summary, offspring born to obese allergic mothers have decreased lung insulin sensitivity and increased lung allergic inflammation. Interestingly, our data also demonstrate that there is both a pregnancy and postpregnancy aspect of maternal allergy and obesity that enhances allergen responsiveness in offspring. [ABSTRACT FROM AUTHOR]

The purpose of the study is to substantiate, based on a review of literary sources, the effectiveness of various types of diet therapy as an initial method of treatment in women with polycystic ovary syndrome and insulin resistance, their effect on the normalization of the menstrual cycle, correction of metabolic disorders and reduction of the level of insulin resistance. From 2018 to 2024 40 articles were analyzed with key words: polycystic ovary syndrome (PCOS), insulin resistance, diet therapy, Mediterranean diet, ketogenic diet, low-carbohydrate diet, low-fat diet, Homeostasis model assessment (HOMA) according to which a review of the available literature was conducted in PubMed, National Library of Medicine, Medscape. The study did not include pregnant, lactating women who took hormonal therapy and/or insulin sensitizers during the last 2 months, had liver, kidney, and heart diseases that failed local treatment of hirsutism, with congenital hyperplasia of the adrenal glands, androgen-secreting tumors, Cushing's syndrome. A review and analysis of studies on the effects of a ketogenic diet for 12 weeks, in which 14 overweight women with a diagnosis of polycystic ovary syndrome, participated. 40 articles were studied using bibliographic and analytical methods. At the beginning of the study patients had HOMA-IR above 2.5, which confirms insulin resistance. After using ketogenic diet, a significant decrease in the level of glucose, insulin, and, therefore, the HOMA index was observed. There were significant changes in lipid profiles with a decrease in triglycerides, total cholesterol, and low-density lipoproteins along with increases in high-density lipoprotein. Anthropometric measurements revealed a weight loss of 8.78 kg and a significant decrease in the body mass index of 3.18. A study of 72 women with PCOS showed a superior efficacy of a Mediterranean diet (MED) combined with a low-carbohydrate (LC) diet versus a low-fat diet alone. In patients who used the combination of MED/LC diet, in 86.7% of cases, the regular menstrual cycle was restored, and pregnancy occurred.

Huizhong Hu, Yuanjie Qiu, Nirui Shen, Huan Chen, Jia Zhang, Yan Wang, Xiangyu Shi, Manxiang Li Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Manxiang Li, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China, Tel\Fax +86-029-85324053, Email manxiangli@hotmail.comPurpose: Although low-carbohydrate and low-fat diets improve weight loss, cardiovascular disease, and diabetes, the relationship between these dietary patterns, highlighting macronutrient sources, and chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to assess the association between low-carbohydrate diets (LCDs) and low-fat diets (LFDs) and the odds of COPD and mortality among people with COPD in the National Health and Nutrition Examination Survey.Patients and Methods: Clinical data were extracted from the 2007– 2008, 2009– 2010, and 2011– 2012 National Health and Nutrition Examination Survey (NHANES) cycles that met the inclusion criteria. Multivariable logistic regression was used to evaluate the associations between LCD and LFD scores and COPD, and multivariable Cox proportional hazards regression and restricted cubic spline (RCS) regression were used to assess the relationship between all-cause mortality and LCD and LFD scores.Results: Comparing extreme tertiles, multivariable-adjusted odds ratio (OR) were 1 (reference), 1.09 (95% CI, 0.77– 1.55), 1.84 (95% CI, 1.09– 3.09) (P = 0.045 for trend) for unhealthy LFD scores. After multivariate adjustment, a per 5-point increase in unhealthy LCD score was associated with a 21% higher risk of total mortality (hazard ratio, 1.21; 95% CI, 1.03– 1.43); while a per 5-point increase in healthy LFD scores was associated with a 21% lower risk of total mortality (HR, 0.79; 95% CI, 0.67– 0.94).Conclusion: Higher unhealthy LFD score was associated with an increased odds of COPD. Unhealthy LCD scores were significantly associated with higher total mortality, whereas healthy LFD scores were associated with lower total mortality in patients with COPD.Keywords: low-carbohydrate diet, low-fat diet, chronic obstructive pulmonary disease, mortality, NHANES

Abstract Purpose Low-fat dietary (LFD) pattern refers to a dietary structure with reduced fat intake. The aim was to investigate the association between LFD pattern and risk of head and neck cancer (HNC). Methods Data were derived from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. LFD score was used to assess adherence to an LFD pattern, with higher scores indicating greater adherence. Cox regression was used to evaluate the association between LFD score and risk of HNC and its subtypes. To visualize the trend in risk of HNC and its subtypes with changing LFD score, restricted cubic spline plots were utilized. A series of subgroup analyses were conducted to identify potential confounders. Sensitivity analyses were performed to assess the robustness of the results. Results Among 98,459 participants of PLCO trial, 268 cases with HNC were identified during an average of 8.8 years of follow-up. In the fully adjusted model, participants in the highest compared with the lowest quartiles of LFD score had a lower risk of HNC (HR Q4 vs. Q1: 0.60; 95% CI: 0.40–0.90; P for trend = 0.026) and larynx cancer (HRQ4 vs. Q1: 0.46; 95% CI: 0.22–0.96; P for trend = 0.039). The restricted cubic spline plots demonstrated a linear dose-response relationship between the LFD score and the risk of HNC and its subtypes (all P for nonlinearity > 0.05). The primary association remained robust in the sensitivity analysis. Conclusion Our findings suggest that adherence to an LFD pattern may lower the risk of HNC in the US population.

Excessive dietary fat intake increases plasma lipid levels and has been associated with reduced bone mineral density (BMD) and increased risk of osteoporotic fracture, especially in older postmenopausal women. The objective of this study was to investigate whether there are sex-related differences in lipid metabolism that could have an impact on large-scale bone regeneration. Because ribs provide a unique exception as the only bones capable of completely regenerating large-scale defects, we used a rib resection mouse model in which human features are recapitulated. After 10 days of exposure to a low-fat diet or high-fat diet (HFD), we performed large-scale rib resection surgeries on male and female mice (6–7 weeks old) with deletion of the low-density lipoprotein (LDL) receptor (Ldlr−/−) and age- and sex-matched wild-type (WT) mice were used as controls. Plasma analysis showed that short-term exposure to HFD significantly increases total cholesterol, LDL cholesterol, and triglycerides levels in Ldlr−/− mice but not in WT, with no differences between males and females. However, under HFD, callus bone volume was significantly reduced exclusively in male Ldlr−/− mice when compared to WT, although these differences were no longer apparent by 21 days after resection. Regardless of diet or genotype, BMD of regenerated ribs did not differ significantly between groups, although male mice typically had lower average BMD values. Together, these results suggest that short-term hyperlipidemia has transient effects on large-scale bone regeneration exclusively in male mice. [ABSTRACT FROM AUTHOR]

Background: Many countries have introduced school food standards to improve the dietary intakes of school-aged children. England has school food standards (SFS) legislation in place but little is known about how well secondary schools comply with this. We aimed to assess compliance with the SFS legislation in English secondary schools and explore the impact of the SFS on pupils' nutritional intake. Methods: We conducted a cross-sectional study with English secondary schools from 2019 to 2022. We compared SFS compliance and pupil nutritional intake in schools mandated or not mandated to comply with the SFS legislation, and explored the association between school compliance and pupil nutritional intake. We assessed the percentage of SFS (%SFS) complied with by reviewing school food menus and observing food served in school canteens. We assessed pupil nutritional intake using a 24-hour dietary recall measure (Intake24) and estimated intakes of free sugar (primary outcome) and other nutrients/foods. We used adjusted multilevel models to compare pupil intakes in the SFS-mandated and SFS-non-mandated schools, and to explore the association between school SFS compliance and pupil intakes. Results: 36 schools (23 not mandated and 13 mandated to comply with the SFS) and 2,273 pupils participated. The median %SFS complied with was 63.9% (interquartile range 60.0–70.0%). This was similar for SFS-non-mandated (64.5%) and SFS-mandated schools (63.3%). Compliance was highest for standards applying to lunchtime (median = 81.3%) and lowest for those applying across the whole school day (median = 41.7%). It was also lower for standards restricting high fat, sugar and energy-dense items (median = 26.1%) than for standards aiming to increase dietary variety (median = 92.3%). Pupils from SFS-mandated schools had a lower mean lunchtime intake of free sugar (g) (adjusted mean difference: -2.78g; 95% CI: -4.66g to -0.90g). There were few significant associations between %SFS complied with and pupil nutritional intake. Conclusions: English secondary schools do not fully comply with SFS legislation regardless of whether they are mandated to comply. Schools and caterers may require monitoring and support to fully comply. There is little evidence that SFS compliance is associated with better pupil nutritional intake. Food environments outside of school also need to be considered. Study registration: ISRCTN68757496 (17-10-2019). [ABSTRACT FROM AUTHOR]

Background: Crohn's disease (CD) is characterized by chronic intestinal inflammation. Diet is a key modifiable factor influencing the gut microbiome (GM) and a risk factor for CD. However, the impact of diet modulation on GM function in CD patients is understudied. Herein, we evaluated the effect of a high-fiber, low-fat diet (the Mi-IBD diet) on GM function in CD patients. All participants were instructed to follow the Mi-IBD diet for 8 weeks. One group of CD patients received one-time diet counseling only (Gr1); catered food was supplied for the other three groups, including CD patients (Gr2) and dyads of CD patients and healthy household controls (HHCs) residing within the same household (Gr3-HHC dyads). Stool samples were collected at baseline, week 8, and week 36, and analyzed by liquid chromatography-tandem mass spectrometry. Results: At baseline, the metaproteomic profiles of CD patients and HHCs differed. The Mi-IBD diet significantly increased carbohydrate and iron transport and metabolism. The predicted microbial composition underlying the metaproteomic changes differed between patients with ileal only disease (ICD) or colonic involvement: ICD was characterized by decreased Faecalibacterium abundance. Even on the Mi-IBD diet, the CD patient metaproteome displayed significant underrepresentation of carbohydrate and purine/pyrimidine synthesis pathways compared to that of HHCs. Human immune-related proteins were upregulated in CD patients compared to HHCs. Conclusions: The Mi-IBD diet changed the microbial function of CD patients and enhanced carbohydrate metabolism. Our metaproteomic results highlight functional differences in the microbiome according to disease location. Notably, our dietary intervention yielded the most benefit for CD patients with colonic involvement compared to ileal-only disease. 9orssYZV9GnhTtyZm1JCtC Video Abstract [ABSTRACT FROM AUTHOR]

Ghrelin is an orexigenic peptide released by gastric ghrelin cells that contributes to obesity and hepatic steatosis. The mechanosensitive ion channel Piezo1 in gastric ghrelin cells inhibits the synthesis and secretion of ghrelin in response to gastric mechanical stretch. We sought to modulate hepatic lipid metabolism by manipulating Piezo1 in gastric ghrelin cells. Mice with a ghrelin cell–specific deficiency of Piezo1 (Ghrl-Piezo1−/−) had hyperghrelinemia and hepatic steatosis when fed a low-fat or high-fat diet. In these mice, hepatic lipid accumulation was associated with changes in gene expression and in protein abundance and activity expected to increase hepatic fatty acid synthesis and decrease lipid β-oxidation. Pharmacological inhibition of the ghrelin receptor improved hepatic steatosis in Ghrl-Piezo1−/− mice, thus confirming that the phenotype of these mice was due to overproduction of ghrelin caused by inactivation of Piezo1. Gastric implantation of silicone beads to induce mechanical stretch of the stomach inhibited ghrelin synthesis and secretion, thereby helping to suppress fatty liver development induced by a high-fat diet in wild-type mice but not in Ghrl-Piezo1−/− mice. Our study elucidates the mechanism by which Piezo1 in gastric ghrelin cells regulate hepatic lipid accumulation, providing insights into potential treatments for fatty liver. Editor's summary: The appetite-stimulating hormone ghrelin promotes hepatic lipid accumulation. Zhang et al. investigated the regulation of hepatic lipid homeostasis by Piezo1, a mechanosensitive ion channel that is activated when food ingestion stretches the stomach and that suppresses ghrelin production. Mice lacking Piezo1 in ghrelin-producing cells in the stomach developed hepatic steatosis, which was reversed by pharmacologically blocking the ghrelin receptor. Gastric bead implantation, which mimicked the mechanical stretch induced by food intake, reduced hepatic steatosis in control mice on a normal diet or with diet-induced obesity but not in the conditional knockout mice. Thus, Piezo1 in ghrelin-producing cells could be targeted to treat metabolic dysfunction–associated steatotic liver disease, the most prevalent liver disorder worldwide. —Wei Wong [ABSTRACT FROM AUTHOR]

Purpose: Low-fat dietary (LFD) pattern refers to a dietary structure with reduced fat intake. The aim was to investigate the association between LFD pattern and risk of head and neck cancer (HNC). Methods: Data were derived from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. LFD score was used to assess adherence to an LFD pattern, with higher scores indicating greater adherence. Cox regression was used to evaluate the association between LFD score and risk of HNC and its subtypes. To visualize the trend in risk of HNC and its subtypes with changing LFD score, restricted cubic spline plots were utilized. A series of subgroup analyses were conducted to identify potential confounders. Sensitivity analyses were performed to assess the robustness of the results. Results: Among 98,459 participants of PLCO trial, 268 cases with HNC were identified during an average of 8.8 years of follow-up. In the fully adjusted model, participants in the highest compared with the lowest quartiles of LFD score had a lower risk of HNC (HR Q4 vs. Q1: 0.60; 95% CI: 0.40–0.90; P for trend = 0.026) and larynx cancer (HRQ4 vs. Q1: 0.46; 95% CI: 0.22–0.96; P for trend = 0.039). The restricted cubic spline plots demonstrated a linear dose-response relationship between the LFD score and the risk of HNC and its subtypes (all P for nonlinearity > 0.05). The primary association remained robust in the sensitivity analysis. Conclusion: Our findings suggest that adherence to an LFD pattern may lower the risk of HNC in the US population. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF), a complex condition arising from impaired ventricular function, necessitates strict adherence to dietary recommendations for optimal patient management. However, information regarding adherence and its influencing factors remains limited. Aim: This study aimed to assess dietary recommendation adherence and its associated factors among HF patients at Southern Ethiopia public hospitals. Methods and results: A cross-sectional study involving 521 participants employed systematic random sampling. Data collection utilized pre-tested, interviewer-administered questionnaires and medical chart reviews. Data were entered and analyzed using Epi Data 3.1 and SPSS 20.0 software. Descriptive statistics were performed. Variables with p-values < 0.25 in binary logistic regression were included in multivariable logistic regression analyses. Statistical significance was set at p < 0.05 with a 95% confidence interval. Results are presented in text, tables, and figures. With a 97.4% response rate, adherence ranged from 20.3% (vegetables and fruits) to 60.3% (fat-free diet). Only 8.1% achieved good adherence across all parameters, with overall adherence at 33.4% (95% CI: 29–37). Multivariable analysis revealed that patients aged 41–60 years (AOR: 1.7), with a history of admission (AOR: 2.5), free from comorbidities (AOR: 0.58), and possessing a favorable attitude (AOR: 0.45) had statistically significant associations with good adherence. Conclusion: Dietary adherence among HF patients remains a challenge. Healthcare providers, particularly those in chronic follow-up settings, should prioritize improving patient attitudes towards proper dietary practices. Tailored education programs targeting younger patients and those free from comorbidities should be implemented. Continuous monitoring, evaluation, and staff recognition for effective client counseling are crucial. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation (> 5% of liver tissue) in the absence of alcohol abuse or other chronic liver diseases. NAFLD can progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). This study aimed to assess the efficacy of probiotic (lactobacillus) supplementation on NAFLD fibrosis score. Methodology: A double-arm randomized controlled trial was conducted in the family medicine clinic of a tertiary hospital, enrolling patients with sonographic evidence of NAFLD. Fifty patients were divided into two groups: the Probiotic group received lifestyle modification instructions along with daily probiotic supplementation for twelve weeks, with regular monthly follow-up visits. The Standard Treatment group received low-fat diet and lifestyle modification instructions only. Results: The mean age of participants was 46.10 years (SD 10.11), with 70% females and 30% males. The study found a statistically significant difference in liver enzymes (ALT and AST) and BMI in the probiotic group before and after intervention. However, there was no significant difference in NAFLD fibrosis score between the two groups. Conclusion: Short-term probiotic treatment resulted in improvements in ALT, AST, and BMI in the probiotic group, but did not significantly affect NAFLD fibrosis score. Further research with larger sample sizes and longer follow-up periods is warranted. Trial registration: The clinical trial was registered at Protocol Registration and Results System with number NCT06074094 (12/09/2021). [ABSTRACT FROM AUTHOR]

Background: Obesity, and in particular abdominal obesity, is associated with an increased risk of developing a variety of chronic diseases. Obesity, aging, and menopause are each associated with differential shifts in the gut microbiome. Obesity causes chronic low-grade inflammation due to increased lipopolysaccharide (LPS) levels which is termed "metabolic endotoxemia." We examined the association of visceral adiposity tissue (VAT) area, circulating endotoxemia markers, and the gut bacterial microbiome in a cohort of aged postmenopausal women. Methods: Fifty postmenopausal women (mean age 78.8 ± 5.3 years) who had existing adipose measurements via dual x-ray absorptiometry (DXA) were selected from the extremes of VAT: n = 25 with low VAT area (45.6 ± 12.5 cm2) and n = 25 with high VAT area (177.5 ± 31.3 cm2). Dietary intake used to estimate the Healthy Eating Index (HEI) score was assessed with a food frequency questionnaire. Plasma LPS, LPS-binding protein (LBP), anti-LPS antibodies, anti-flagellin antibodies, and anti-lipoteichoic acid (LTA) antibodies were measured by ELISA. Metagenomic sequencing was performed on fecal DNA. Female C57BL/6 mice consuming a high-fat or low-fat diet were treated with 0.4 mg/kg diet-derived fecal isolated LPS modeling metabolic endotoxemia, and metabolic outcomes were measured after 6 weeks. Results: Women in the high VAT group showed increased Proteobacteria abundance and a lower Firmicutes/Bacteroidetes ratio. Plasma LBP concentration was positively associated with VAT area. Plasma anti-LPS, anti-LTA, and anti-flagellin IgA antibodies were significantly correlated with adiposity measurements. Women with high VAT showed significantly elevated LPS-expressing bacteria compared to low VAT women. Gut bacterial species that showed significant associations with both adiposity and inflammation (anti-LPS IgA and LBP) were Proteobacteria (Escherichia coli, Shigella spp., and Klebsiella spp.) and Veillonella atypica. Healthy eating index (HEI) scores negatively correlated with % body fat and anti-LPS IgA antibodies levels. Preclinical murine model showed that high-fat diet-fed mice administered a low-fat diet fecal-derived LPS displayed reduced body weight, decreased % body fat, and improved glucose tolerance test parameters when compared with saline-injected or high-fat diet fecal-derived LPS-treated groups consuming a high-fat diet. Conclusions: Increased VAT in postmenopausal women is associated with elevated gut Proteobacteria abundance and immunogenic metabolic endotoxemia markers. Low-fat diet-derived fecal-isolated LPS improved metabolic parameters in high-fat diet-fed mice giving mechanistic insights into potential pro-health signaling mediated by under-acylated LPS isoforms. 7yVbQmTTfsF9b4Af3tznWN Video Abstract [ABSTRACT FROM AUTHOR]

Ketogenic diets (KDs) are very high in fat and low in carbohydrates. Evidence supports that KDs improve glucose metabolism in humans and rodents that are obese and/or insulin resistant. Conversely, findings in healthy rodents suggest that KDs may impair glucose homeostasis. In addition, most experimental KDs are composed of saturated and monounsaturated fatty acids, with almost no omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA). Evidence supports a beneficial role for n-3 LCPUFA on glucose homeostasis in the context of a metabolic challenge. To our knowledge, no study has examined whether the inclusion of n-3 LCPUFA affects the impact of a KD on glucose homeostasis. The objective of this study was to examine the impact of a KD on whole body glucose tolerance and skeletal muscle insulin response in rats and to determine if increasing the n-3 LCPUFA content in a KD with menhaden oil could improve metabolic outcomes. Male Sprague-Dawley rats were pair-fed one of a low-fat diet, high-fat diet, KD, or a KD supplemented with menhaden oil for 8 wk. No significant differences in whole body glucose tolerance, skeletal muscle insulin signaling, or skeletal muscle insulin-stimulated glucose uptake were detected between the dietary groups. Our findings suggest that KD feeding, with or without supplementation of n-3 LCPUFA, does not affect whole body glucose homeostasis or skeletal muscle insulin response under pair-feeding conditions. NEW & NOTEWORTHY: Ketogenic diets (KDs) improve glucose metabolism in humans and rodents that are insulin resistant, but their impact is unclear in a healthy context. Furthermore, standard KDs typically lack beneficial omega-3 long-chain polyunsaturated fatty acids (n3-LCPUFA). This study assessed whether supplementing a KD with n3-LCPUFA could alter glucose homeostasis or skeletal muscle insulin response. No differences were observed between a standard KD and a KD with n3-LCPUFA when energy intake was controlled. [ABSTRACT FROM AUTHOR]

Simple Summary: Lifestyle dietary changes implemented by people who are overweight or obese to improve health generally focus on caloric restriction, changes in macronutrient intake, or both. Findings from reports of the impact of these changes on cancer are mixed, with many subjected to secondary analysis bias. An impact on cancer endpoints requires long-term (≥1 year) intervention. There is a clear need for more reports evaluating the role of diet in cancer risk reduction in overweight/obese individuals who are at increased risk of obesity-related cancers, especially reports focusing on cancers other than breast. Pharmacologic and metabolic/bariatric surgery-MBS strategies have demonstrated promise to deliver both greater initial weight loss and better weight loss maintenance). The impact of weight loss on reducing cancer risk may depend on the (1) amount and (2) maintenance of weight loss. Background: Most randomized controlled trials (RCTs) assessing the impact of diet on cancer have been short term (<1 year), mostly evaluating breast cancer survivors. Given the many-year interval that is generally required for an intervention to have an impact on cancer risk or prognosis, as well as the fact that lifestyle strategies such as diet modification frequently fail due to lack of adherence over the long term, we focused this systematic review only on longer-term (≥1 year) intervention reports. Diet intervention reports focused on reducing cancer risk in overweight and obese individuals target caloric restriction (every day, some days, or most hours of each day). Methods: This study is a systematic review of RCTs lasting at least 1 year, testing dietary interventions with a primary or secondary endpoint of cancer or a biomarker linked to cancer. Results: Fifty-one reports met our review criteria. Twenty of fifty-one (39%) reports are RCTs where the primary endpoint was cancer or a cancer-related biomarker, while the other reports evaluated reports where cancer or a cancer-related biomarker was a secondary endpoint. Thirteen of twenty (65%) primary reports evaluated isocaloric, and the remaining eight evaluated low-calorie diets. All but one of the primary and two secondary isocaloric diet reports evaluated the benefit of a low-fat diet (LFD), with the other three evaluating a Mediterranean diet (MedD). More LCD vs. isocaloric diet primary reports (71% vs. 38%) demonstrated cancer or cancer-related biomarker benefit; the difference in chance of benefit with secondary reports was 85% for LCD vs. 73% for isocaloric diets. Three of three MedD reports demonstrated benefit. Sixty-nine percent (20/29) of the secondary reports came from two large reports: the WHI diet modification trial (15 secondary reports) and the polyp prevention trial (5 secondary reports). Nineteen of twenty-two (86%) primary reports enrolled only women, and three enrolled both men and women. No study that met our criteria enrolled only men, comprising 1447 men in total vs. 62,054 women. Fifteen of twenty (75%) primary reports focus on healthy women or women with breast cancer. Adherence findings are discussed when provided. Conclusions: More long-term RCTs evaluating cancer and cancer-related biomarker endpoints are needed, especially for cancers at sites other than the breast. [ABSTRACT FROM AUTHOR]

Over recent decades, dietary patterns have changed significantly due to the increasing availability of convenient, ultra-processed refined foods. Refined foods are commonly depleted of key bioactive compounds, which have been associated with several deleterious health conditions. As the gut microbiome can influence the brain through a bidirectional communication system known as the 'microbiota-gut-brain axis', the consumption of refined foods has the potential to affect cognitive health. In this study, multi-omics approaches were employed to assess the effect of a refined diet on the microbiota-gut-brain axis, with a particular focus on bile acid metabolism. Mice maintained on a refined low-fat diet (rLFD), consisting of high sucrose, processed carbohydrates and low fibre content, for eight weeks displayed significant gut microbial dysbiosis, as indicated by diminished alpha diversity metrics (p < 0.05) and altered beta diversity (p < 0.05) when compared to mice receiving a chow diet. Changes in gut microbiota composition paralleled modulation of the metabolome, including a significant reduction in short-chain fatty acids (acetate, propionate and n-butyrate; p < 0.001) and alterations in bile acid concentrations. Interestingly, the rLFD led to dysregulated bile acid concentrations across both the colon (p < 0.05) and the brain (p < 0.05) which coincided with altered neuroinflammatory gene expression. In particular, the concentration of TCA, TDCA and T-α-MCA was inversely correlated with the expression of NF-κB1, a key transcription factor in neuroinflammation. Overall, our results suggest a novel link between a refined low-fat diet and detrimental neuronal processes, likely in part through modulation of the microbiota-gut-brain axis and bile acid dysmetabolism. [ABSTRACT FROM AUTHOR]

The purpose of the study is to substantiate, based on a review of literary sources, the effectiveness of various types of diet therapy as an initial method of treatment in women with polycystic ovary syndrome and insulin resistance, their effect on the normalization of the menstrual cycle, correction of metabolic disorders and reduction of the level of insulin resistance. From 2018 to 2024 40 articles were analyzed with key words: polycystic ovary syndrome (PCOS), insulin resistance, diet therapy, Mediterranean diet, ketogenic diet, low-carbohydrate diet, low-fat diet, Homeostasis model assessment (HOMA) according to which a review of the available literature was conducted in PubMed, National Library of Medicine, Medscape. The study did not include pregnant, lactating women who took hormonal therapy and/or insulin sensitizers during the last 2 months, had liver, kidney, and heart diseases that failed local treatment of hirsutism, with congenital hyperplasia of the adrenal glands, androgen-secreting tumors, Cushing's syndrome. A review and analysis of studies on the effects of a ketogenic diet for 12 weeks, in which 14 overweight women with a diagnosis of polycystic ovary syndrome, participated. 40 articles were studied using bibliographic and analytical methods. At the beginning of the study patients had HOMA-IR above 2.5, which confirms insulin resistance. After using ketogenic diet, a significant decrease in the level of glucose, insulin, and, therefore, the HOMA index was observed. There were significant changes in lipid profiles with a decrease in triglycerides, total cholesterol, and low-density lipoproteins along with increases in high-density lipoprotein. Anthropometric measurements revealed a weight loss of 8.78 kg and a significant decrease in the body mass index of 3.18. A study of 72 women with PCOS showed a superior efficacy of a Mediterranean diet (MED) combined with a low-carbohydrate (LC) diet versus a low-fat diet alone. In patients who used the combination of MED/LC diet, in 86.7% of cases, the regular menstrual cycle was restored, and pregnancy occurred. [ABSTRACT FROM AUTHOR]

In the study of obesity and diabetes, mice are widely used for experimental research, and fasting is a common procedure used to reset metabolism in mouse models. The fasting duration for experimental mice varies greatly in nutritional and metabolic studies, ranging from 2 to 48 h. This study aims to assess the optimal fasting duration for mice fed low- and high-fat diets over a short period of time. C57BL/6J mice were fed a low-fat diet (LFD) or high-fat diet (HFD) and fasted for 4, 6, 8, 10, 12, or 24 h. The effects of different conditions after fasting on the metabolic level of mice were explored, and the data were collected for analysis. Our data indicate that fasting has inconsistent effects on mice fed a low-fat or high-fat diet. To compare the metabolic differences between mice in different dietary levels and thereby secure better scientific data, mice should fast for 6 h in animal experiments. Fasting for 6 h is also recommended when comparing glucose tolerance with insulin tolerance. [ABSTRACT FROM AUTHOR]

Background: Progressive familial intrahepatic cholestasis is an autosomal recessive genetic disorder that manifests primarily with jaundice and pruritus and can progresses from persistent cholestasis to cirrhosis and late childhood liver failure. Classically, progressive familial intrahepatic cholestasis is classified into three subtypes: 1, 2, and 3 and results from a defect in a biliary protein responsible for bile formation and circulation in the liver. In the last decade and with the increased use of genetic testing, more types have been known. Case presentation: A 6-month-old Afrocentric boy presented with progressive jaundice and pruritus that started since the age of 2 months. He was thoroughly investigated to be finally diagnosed as progressive familial intrahepatic cholestasis type 4. A low-fat diet, ursodeoxycholic acid, fat-soluble vitamins, and cholestyramine were started. He showed initial improvement then had refractory pruritus and impaired quality of life. He underwent surgical biliary diversion at the age of 1 year with marked improvement of manifestations. Conclusion: Owing to the increased technology of genetic testing, more clinical subtypes of progressive familial intrahepatic cholestasis were diagnosed other than the classical three types. Surgical management using biliary diversion could be beneficial and delays or may even obviate the need for liver transplantation. [ABSTRACT FROM AUTHOR]

Poor nutrition is a risk factor for dental decay in younger people. However, except for sugar, it is unclear if this is true in older age groups. The aim of this study was to analyze the possible associations between overall dietary intake of nutrients and diet quality and the presence of dental decay in community-dwelling older men. A cross-sectional analysis of a longitudinal study with a standardized validated diet history assessment and comprehensive oral health examination in 520 community-dwelling men (mean age: 84 years) participating in the Concord Health and Ageing in Men Project. Nutrient reference values were used to determine if individual micronutrients and macronutrients were meeting recommendations. Acceptable macronutrient distribution ranges (AMDRs) were attained for fat and carbohydrate intakes and were incorporated into a dichotomous variable to determine if the participants were consuming a high fat-low carbohydrate diet. Diagnosis of coronal caries was based on visual criteria and inspection and was completed on each of the five coronal surfaces. Root surface caries was textual changes across four root surfaces. This diagnosis was used to categorize participants by the presence and severity of coronal and root caries. The adjusted logistic regression showed not meeting the recommended intakes for thiamin (odds ratio [OR]: 2.32 95% confidence interval [CI] 1.15–4.67), and zinc (OR: 3.33, 95% CI: 1.71–6.48) were associated with presence of severe root decay. Adjusted analysis also showed that participants who were outside the recommended AMDR for fat (OR: 0.61, 95% CI: 0.38–0.98) and those who consumed a high fat and low carbohydrate diet (OR: 0.56, 95% CI: 0.35–0.91) were less likely to have coronal tooth decay. Our study shows associations between micronutrients and macronutrients and coronal and root surface decay. Although this study cannot prescribe causality or be generalized to all older adults, diet has a possible association with dental decay in older men. [ABSTRACT FROM AUTHOR]

Background: Constipation impacts health-related quality of life with a burden similar to other chronic conditions. This study characterises the prevalence of constipation and its associated factors in older adults with intellectual disability. Methods: Data from the Intellectual Disability Supplement of The Irish Longitudinal Study on Ageing was analysed using bivariate and multivariate approaches. Results: Constipation affected 43.5% of this cohort and was more common in females, those in residential settings, and those with a severe/profound level of intellectual disability. The type of residence, level of intellectual disability, a low fat diet, high cholesterol, multimorbidity and, physical activity predicted constipation status with 67.7% accuracy. Physical activity was associated with lower constipation prevalence, where minimal activity was sufficient to observe this effect. Conclusions: Constipation is a common health concern in older people with intellectual disability. This analysis reveals characteristics that should inform the careful monitoring of bowel health in this population. [ABSTRACT FROM AUTHOR]

The antidiabetic drug metformin has a wide range of metabolic effects and may also reduce the risk of obesity-related diseases. The aim of the current study was to investigate if metformin could counteract meldonium-induced fatty liver. Four groups of male C57BL/6J mice were fed a low-fat control diet, or low-fat diets supplemented with metformin, meldonium, or metformin and meldonium for three weeks. Meldonium treatment led to 5.2-fold higher hepatic triacylglycerol (TAG) levels compared to control, and metformin lowered the meldonium-induced lipid accumulation insignificantly by 21%. Mice treated with metformin and meldonium demonstrated significantly lower weight gain, visceral adipose tissue weight and plasma levels of TAG compared to meldonium alone. The hepatic mRNA level of carnitine palmitoyl transferase 1 was increased 2-fold with combined meldonium and metformin treatment compared to meldonium treatment (p < 0.001). Increased hepatic expression of genes involved in fatty acid oxidation and lipid transport was observed in the combination group compared to control, and increased gene expression of the mitochondrial uncoupling protein UCP2 was observed compared to the meldonium group. In addition, the product of fatty acid oxidation, acetylcarnitine, increased in plasma in metformin-treated mice. Altogether, metformin treatment influenced hepatic lipid metabolism and lowered plasma TAG in meldonium-induced fatty liver in mice. [ABSTRACT FROM AUTHOR]

Some health disorders, such as obesity and type 2 diabetes, are associated with a poor diet and low quality of the fat in it. The type and duration of the diet have an impact on the liver. This investigation uses the proteomic approach to identify changes in the mouse liver protein profile in adaptation to high-fat diets with different saturated fatty acid contents and linoleic acid (18:2n-6) to α-linolenic acid (18:3n-3) fatty acid ratios. Four groups of male mice were fed different diets: one standard diet and three high-fat diets were investigated. After six months on these diets, the animals were sacrificed for liver dissection. Two-dimensional electrophoresis was used to separate the complex liver protein mixture, which enabled the separation of proteins against a wide, 3–10 range of pH and molecular weights of 15–250 kDa. Protein profiles were analysed in the PDQuest Advanced 8.0.1 program. Differentially expressed spots were identified using matrix-assisted laser desorption/ionisation–time-of-flight tandem mass spectrometry and peptide mass fingerprinting. The levels of identified proteins were validated using Western blotting. Transcript levels were evaluated using a real-time quantitative PCR. The analysis of mouse liver protein profiles enabled the identification of 32 protein spots differing between nutritional groups. A diet high in polyunsaturated fatty acids modulated the levels of liver proteins involved in critical metabolic pathways, including amino acid metabolism, carbohydrate metabolism and cellular response to oxidative stress. [ABSTRACT FROM AUTHOR]

A 12-week-old male Australian Kelpie was referred for nutritional consultation after being diagnosed with autosomal recessively inherited intestinal lipid malabsorption (ILM). At the timepoint of referral, the dog's bodyweight was below the ideal growth curve, the faecal quality was poor and the patient received a pancreatic enzyme supplement. The patient's diet at referral was based on a commercial dry food for all age groups and contained approximately 20% fat in dry matter (DM). We formulated a highly digestible homemade diet with a low-fat content (10% DM) while meeting the recommendations for linoleic acid, a-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid, which supported the nutritional requirements of a growing dog with impaired fat absorption. The diet was adapted according to the different growth phases. To our knowledge, this is the first case report highlighting the nutritional management of an Australian Kelpie with ILM. After diet adaptation, the patient reached his growth potential. [ABSTRACT FROM AUTHOR]

Weight loss can positively alter female physiology; however, whether dietary carbohydrate- or fat- restriction confer unique effects is less studied. Precisely designed, hypocaloric well-formulated ketogenic diets (KD; ~75% energy for weight maintenance) were compared to isocaloric/isonitrogenous low-fat diet (LFD) on self-reported menses in pre-menopausal overweight and obese women (mean ± SD: 34 ± 10 years, BMI: 32.3 ± 2.7 kg/m2). Women received a precisely-weighed and formulated KD with either twice-daily with ketone salts (KS; n = 6) or a flavor-matched placebo (PL; n = 7) daily for six-weeks. An age and BMI-matched cohort (n = 6) was later assigned to the LFD and underwent the same testing procedures as the KD. Self-reported menses fluctuations were assessed bi-weekly along with measures of body weight, body composition, and fasting serum clinical chemistries using repeated measures ANOVA with Bonferroni post-hoc corrections. Both diets elicited clinically-significant weight-loss (Δ: -7.0 ± 0.5 kg; p < 0.001), primarily from fat-mass (Δ: -4.6 ± 0.3 kg; p < 0.001), and improved insulin-sensitivity and serum lipids (all p < 0.05). Fasting plasma glucose and inflammatory markers were not different between diets. Fasting capillary beta-hydroxybutyrate (R-βHB) increased significantly during the KD, independent of supplementation (Δ: 1.2 ± 0.3 mM R-βHB; p < 0.001). Women randomized to the KD+KS (30%) and KD+PL (43%) reported subjective increases in menses frequency and intensity after 14 days, whereas another third reported a regain of menses (>1 year since the last period) after 28 days. No LFD participants reported menses changes. Nutrient-dense, whole-food KDs and LFD improved weight, BMI, body composition, and blood parameters in pre-menopausal women after six-weeks. Changes in self-reported menses were described by most of the KD participants, but none of the LFD women suggesting there may be unique effects of nutritional ketosis, independent of weight loss. [ABSTRACT FROM AUTHOR]

Maternal obesity during pregnancy is associated with adverse pregnancy outcomes. This might be due to undesired obesity-induced changes in the maternal gut microbiota and related changes in the maternal immune adaptations during pregnancy. The current study examines how obesity affects gut microbiota and immunity in pregnant obese and lean mice during mid-pregnancy (gestational day 12 (GD12)). C57BL/6 mice were fed a high-fat diet or low-fat diet from 8 weeks before mating and during pregnancy. At GD12, we analyzed the gut microbiota composition in the feces and immune responses in the intestine (Peyer's patches, mesenteric lymph nodes) and the peripheral circulation (spleen and peripheral blood). Maternal obesity reduced beneficial bacteria (e.g., Bifidobacterium and Akkermansia) and changed intestinal and peripheral immune responses (e.g., dendritic cells, Th1/Th2/Th17/Treg axis, monocytes). Numerous correlations were found between obesity-associated bacterial genera and intestinal/peripheral immune anomalies. This study shows that maternal obesity impacts the abundance of specific bacterial gut genera as compared to lean mice and deranges maternal intestinal immune responses that subsequently change peripheral maternal immune responses in mid-pregnancy. Our findings underscore the opportunities for early intervention strategies targeting maternal obesity, ideally starting in the periconceptional period, to mitigate these obesity-related pregnancy effects. [ABSTRACT FROM AUTHOR]

Background: High-fat diets (HFD) are known to enhance feed conversion ratio in broiler chickens, yet they can also result in hepatic fat accumulation. Bile acids (BAs) and gut microbiota also play key roles in the formation of fatty liver. In this study, our objective was to elucidate the mechanisms through which BA supplementation reduces hepatic fat deposition in broiler chickens, with a focus on the involvement of gut microbiota and liver BA composition. Results: Newly hatched broiler chickens were allocated to either a low-fat diet (LFD) or HFD, supplemented with or without BAs, and subsequently assessed their impacts on gut microbiota, hepatic lipid metabolism, and hepatic BA composition. Our findings showed that BA supplementation significantly reduced plasma and liver tissue triglyceride (TG) levels in 42-day-old broiler chickens (P < 0.05), concurrently with a significant decrease in the expression levels of fatty acid synthase (FAS) in liver tissue (P < 0.05). These results suggest that BA supplementation effectively diminishes hepatic fat deposition. Under the LFD, BAs supplementation increased the BA content and ratio of Non 12-OH BAs/12-OH BAs in the liver and increased the Akkermansia abundance in cecum. Under the HFD, BA supplementation decreased the BAs and increased the relative abundances of chenodeoxycholic acid (CDCA) and cholic acid (CA) in hepatic tissue, while the relative abundances of Bacteroides were dramatically reduced and the Bifidobacterium, Escherichia, and Lactobacillus were increased in cecum. Correlation analyses showed a significant positive correlation between the Akkermansia abundance and Non 12-OH BA content under the LFD, and presented a significant negative correlation between the Bacteroides abundance and CA or CDCA content under the HFD. Conclusions: The results indicate that supplementation of BAs in both LFD and HFD may ameliorate hepatic fat deposition in broiler chickens with the involvement of differentiated microbiota–bile acid profile pathways. [ABSTRACT FROM AUTHOR]

It had been observed that homozygous albumin knockout mice (Alb−/−) exhibit low plasma free fatty acid (FFA) concentration and improved blood glucose regulation. However, it was not yet known to what extent heterozygous albumin knockout (Alb+/−) mice would display a similar phenotype. Alb−/−, Alb+/−, and wild-type (WT) female mice were studied on a low-fat diet (LFD) or high-fat diet (HFD). On both diets, decreased plasma FFA concentration, and improved glucose tolerance test were observed in Alb−/−, but not in Alb+/−, compared to WT. Plasma adiponectin concentration showed greater elevation in Alb−/− than Alb+/−. Consistent with that, adiponectin gene expression was significantly higher in Alb−/− mice than in Alb+/− and WT mice. A dose-dependent response was observed for hepatic Acadl gene expression showing higher Acadl gene expression in Alb−/− mice than in Alb+/− and WT mice. In conclusion, although female Alb+/− mice exhibited some slight differences from WT mice (e.g., increased plasma adiponectin and hepatic Acadl gene expression), Alb+/− mice did not exhibit improved glucoregulation in comparison to WT mice, indicating that a minor suppression of albumin expression is not sufficient to improve glucoregulation. Furthermore, it is now clear that although the response of female mice to HFD might be unique from how males generally respond, still the complete albumin deficiency in Alb−/− mice and the associated FFA reduction is capable of improving glucoregulation in females on this diet. The present results have implications for the role of albumin and FFA in the regulation of metabolism. [ABSTRACT FROM AUTHOR]

Chyloperitoneum is the presence of chyle in the peritoneal cavity. This study focuses on acute chyloperitoneum, a rare condition with an unclear incidence due to limited number of reported cases in the literature. Here, we present a 24-year-old Saudi female with chyloperitoneum diagnosed intraoperatively during a laparoscopic appendectomy for acute appendicitis that was managed successfully with a low-fat diet and drainage, alongside a literature review to elucidate the condition's pathophysiology and therapeutic strategies. A conservative management approach is recommended for acute chyloperitoneum in the context of appendicitis, this includes intraperitoneal drainage, appendectomy when needed, and careful observation. Our proposed management strategy aligns with findings from the literature review and supports conservative management as a safe and effective treatment modality for this rare condition. [ABSTRACT FROM AUTHOR]

Background: Imbalances in gut microbiota and subsequent destabilization of intestinal barrier equilibrium have been related to the evolution of metabolic disorders. Goji berries (Lycium barbarum; GB) and their fermented counterpart (FGB) have been identified for their prebiotic capacity in managing intestinal barrier functions and inflammatory profiles Consequently, this research was designed to investigate the effects of supplementing GB and FGB on intestinal integrity, inflammation, and changes in the composition of gut microbiota in high-fat (HF)-fed rats. Materials and Methods: Thirty-two male Sprague–Dawley rats (6 weeks old, 8 per group) were divided into four categories based on their weight and provided with either respective diets over a 6-week period: low-fat (LF; 10% of calories from fat), HF (45% of calories from fat), and HF diets supplemented with either GB or FGB at a 2% (w/w). Results: Supplementation of GB and FGB resulted in compositional changes in the gut microbiota, denoted by a distinct abundance of Faecalibacterium prausnitzii with GB and Akkermansia muciniphila species with FGB, which have been linked to ameliorated obesity phenotypes and metabolic parameters. These alterations were correlated with enhancements in gut barrier integrity, thereby protecting against local and systemic inflammation induced by a HF diet. Supplementation with GB and FGB also mitigated lipopolysaccharide-induced inflammation through inhibition of its downstream pathway. Conclusion: These findings indicate that both GB and FGB supplementation can improve gut barrier function and inflammatory profiles in HF-fed rats via modulation of the microbial composition of the gut, supporting the potential application of GB and FGB in improving gut barrier function and managing inflammation amid metabolic challenges. [ABSTRACT FROM AUTHOR]

Inhibition of sodium-glucose cotransporter 2 (SGLT2) by empagliflozin (EMPA) and other “flozins” can improve glycemic control under conditions of diabetes and kidney disease. Though they act on the kidney, they also offer cardiovascular and liver protection. Previously, we found that EMPA decreased circulating triglycerides and hepatic lipid and cholesterol esters in male TallyHo mice fed a high-milk-fat diet (HMFD). The goal of this study was to determine whether the liver protection is associated with a change in metabolic function by characterizing the hepatic and circulating metabolic and lipidomic profiles using targeted LCMS. In both male and female mice, HMFD feeding significantly altered the circulating and hepatic metabolome compared with low-fat diet (LFD). Addition of EMPA resulted in the restoration of circulating orotate (intermediate in pyrimidine biosynthesis) and hepatic dihydrofolate (intermediate in the folate and methionine cycles) levels in males and acylcarnitines in females. These changes were partially explained by altered expression of rate-limiting enzymes in these pathways. This metabolic signature was not detected when EMPA was incorporated into an LFD, suggesting that the restoration requires the metabolic shift that accompanies the HMFD. Notably, the HMFD increased expression of 18 of 20 circulating amino acids in males and 11 of 20 in females, and this pattern was reversed by EMPA. Finally, we confirmed that SGLT2 inhibition upregulates ketone bodies including b-hydroxybutyrate. Collectively, this study highlights the metabolic changes that occur with EMPA treatment, and sheds light on the possible mechanisms by which this drug offers liver and systemic protection. NEW & NOTEWORTHY Sodium-glucose cotransporter 2 (SGLT2) inhibitors, including empagliflozin, have emerged as a new treatment option for individuals with type 2 diabetes that have positive impacts on kidney and cardiovascular disease. However, less is known about their impact on other tissues, including the liver. Here, we report that empagliflozin reduces hepatic steatosis that is associated with restoring metabolic intermediates in the folate and pyrimidine biosynthesis pathways. These changes may lead to new approaches to treat nonalcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]

Purpose: Maternal and postnatal overnutrition has been linked to an increased risk of cardiometabolic diseases in offspring. This study investigated the impact of adult-onset voluntary wheel running to counteract cardiometabolic risks in female offspring exposed to a life-long high-fat, high-sucrose (HFHS) diet. Methods: Dams were fed either an HFHS or a low-fat, low-sucrose (LFLS) diet starting from 8 wk before pregnancy and continuing throughout gestation and lactation. Offspring followed their mothers' diets. At 15 wk of age, they were divided into sedentary (Sed) or voluntary wheel running (Ex) groups, resulting in four groups: LFLS/Sed (n = 10), LFLS/Ex (n = 5), HFHS/Sed (n = 6), HFHS/Ex (n = 5). Cardiac function was assessed at 25 wk, with tissue collection at 26 wk for mitochondrial respiratory function and protein analysis. Data were analyzed using two-way ANOVA. Results: Although maternal HFHS diet did not affect the offspring's body weight at weaning, continuous HFHS feeding postweaning resulted in increased body weight and adiposity, irrespective of the exercise regimen. HFHS/Sed offspring showed increased left ventricular wall thickness and elevated expression of enzymes involved in fatty acid transport (CD36, FABP3), lipogenesis (DGAT), glucose transport (GLUT4), oxidative stress (protein carbonyls, nitrotyrosine), and early senescence markers (p16, p21). Their cardiac mitochondria displayed lower oxidative phosphorylation (OXPHOS) efficiency and reduced expression of OXPHOS complexes and fatty acid metabolism enzymes (ACSL5, CPT1B). However, HFHS/Ex offspringmitigated these effects, aligning more with LFLS/Sed offspring. Conclusions: Adult-onset voluntary wheel running effectively counteracts the detrimental cardiac effects of a lifelong HFHS diet, improving mitochondrial efficiency, reducing oxidative stress, and preventing early senescence. This underscores the significant role of physical activity in mitigating diet-induced cardiometabolic risks. [ABSTRACT FROM AUTHOR]