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Background and aim: Telomere length (TL) is a key biomarker of cellular aging, with shorter telomeres associated with age-related diseases. Lifestyle interventions mitigating telomere shortening are essential for preventing such conditions. This study aimed to examine the effects of two weight loss dietary strategies, based on a moderately high-protein (MHP) diet and a low-fat (LF) diet on TL in individuals with overweight or obesity. Methods and Results: A total of 164 participants, aged 18–65 years from the OBEKIT trial received the MHP (n = 83) or the LF diet (n = 81) for 4 months and had TL data for analyses. TL was measured at baseline and after 4 months of the intervention using monochrome multiplex quantitative polymerase chain reaction (MMqPCR). Both groups experienced significant improvements in anthropometric and biochemical parameters after the dietary intervention (p < 0.001). The MHP group showed an increase in TL (+0.16 ± 0.13) compared to the LF group (−0.05 ± 0.13) in multiple-adjusted models (p = 0.016). An interaction was observed between the sex and dietary group, where women in the MHP group had increased TL (+0.23 ± 0.16) after 4 months compared to women in the LF group (−0.13 ± 0.15; p = 0.001); no differences between dietary groups were found in men. This increase in TL for women was associated with an increase in protein intake (p = 0.006), measured through dietary questionnaires. Conclusion: This study shows that a MHP diet may have a protective effect on TL during weight loss, particularly in women, potentially contributing to healthier aging. These results highlight the importance of considering macronutrient composition in dietary interventions aimed at preserving TL. [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]

Background: This observational cross-sectional study was designed to explore the effects of a low-carbohydrate diet (LCD) and a low-fat diet (LFD) on metabolic-dysfunction-associated fatty liver disease (MAFLD). Methods: This study involved 3961 adults. The associations between LCD/LFD scores and MAFLD were evaluated utilizing a multivariable logistic regression model. Additionally, a leave-one-out model was applied to assess the effect of isocaloric substitution of specific macronutrients. Results: Participants within the highest tertile of healthy LCD scores (0.63; 95% confidence interval [CI], 0.45–0.89) or with a healthy LFD score (0.64; 95%CI, 0.48–0.86) faced a lower MAFLD risk. Furthermore, compared with tertile 1, individuals with unhealthy LFD scores in terile 2 or tertile 3 had 49% (95%CI, 1.17–1.90) and 77% (95%CI, 1.19–2.63) higher risk levels for MAFLD, respectively. Conclusions: Healthy LCD and healthy LFD are protective against MAFLD, while unhealthy LFD can increase the risk of MAFLD. Both the quantity and quality of macronutrients might have significant influences on MAFLD. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is the first cause of chronic liver disease and is also associated with other harmful entities such as obesity, metabolic syndrome, dyslipidemia, and diabetes. NAFLD is a significant public health concern worldwide, impacting individuals of all ages, and its prevalence is projected to increase in the near future due to its connection with obesity. Intrinsic (genetics) and external (lifestyle) factors may also modulate NAFLD, and, in turn, may partly explain the observed relationship between NAFLD and cardiovascular disease (CVD). Although many drugs are been tested to treat NAFLD, to date, no drug has indication to specifically treat this disorder. Thus, the current management of NAFLD relies on lifestyle modifications and specifically on weight loss, physical activity, and the intake of a healthy diet. In the present narrative review, we will discuss the effects of certain dietary patterns on NAFLD incidence and progression. [ABSTRACT FROM AUTHOR]

3-Hydroxy-3-Methylglutaryl-CoA Lyase (HMGCL) deficiency can be a very severe disorder that typically presents with acute metabolic decompensation with features of hypoketotic hypoglycemia, hyperammonemia, and metabolic acidosis. A retrospective chart and literature review of Australian patients over their lifespan, incorporating acute and long-term dietary management, was performed. Data from 10 patients contributed to this study. The index case of this disorder was lost to follow-up, but there is 100% survival in the remainder of the cases despite several having experienced life-threatening episodes. In the acute setting, five of nine patients have used 900 mg/kg/day of sodium D,L 3-hydroxybutyrate in combination with intravenous dextrose-containing fluids (delivering glucose above estimated basal utilization requirements). All patients have been on long-term protein restriction, and those diagnosed more recently have had additional fat restriction. Most patients take L-carnitine. Three children and none of the adults take nocturnal uncooked cornstarch. Of the cohort, there were two patients that presented atypically—one with fulminant liver failure and the other with isolated developmental delay. Dietary management in patients with HMGCL deficiency is well tolerated, and rapid institution of acute supportive metabolic treatment is imperative to optimizing survival and improve outcomes in this disorder. [ABSTRACT FROM AUTHOR]

Diets for healthy aging have long been an intriguing issue. The current study makes a head-to-head comparison of four dietary patterns and their associations with soluble Klotho (s-Klotho) levels, an aging-related marker. The dietary data of 7906 subjects were obtained from the National Health and Nutrition Examination Survey 2007–2016. Each participant was given a score or was grouped according to four dietary patterns, namely the Mediterranean adherence diet score (MDS), the low-carbohydrate-diet score, a low-fat diet, and a low-carbohydrate diet. Subsequently, the associations with s-Klotho were examined using linear regression analyses. In addition, we calculated the odds ratio (OR) for aging in different dietary patterns, taking the lowest quartile of s-Klotho as a reference for aging. The MDS was the only dietary pattern that revealed a relationship with s-Klotho levels. The positive association (β coefficient: 9.41, p < 0.001) remained significant when dividing the MDS into tertiles (Tertile 2: β coefficient: 36.87, p < 0.001; Tertile 3: β coefficient: 45.92, p < 0.001) and grouping participants into subsets by sex, age, and BMI. A lower OR for aging was observed in higher MDS groups (Tertile 2: OR = 0.86, p = 0.026; Tertile 3: OR = 0.77, p < 0.001). However, when analyzed separately, merely three out of nine components of the MDS, namely alcohol consumption (β coefficient: 42.54, p < 0.001), fruit (β coefficient: 11.59, p = 0.029), and dairy products (β coefficient: 8.55, p = 0.032), showed a significant association with s-Klotho. The Mediterranean diet adopts a food-based approach, which has the merit of valuing the complex interactions between foods and their constituents, and further brings benefits to healthy aging. [ABSTRACT FROM AUTHOR]

Background: Cataract is a leading cause of vision impairment worldwide, and surgery is the only available treatment. The process that initiates lens opacification is dependent on the oxidative stress experienced by the lens components. A healthy overall dietary pattern, with the potential to reduce oxidative stress, has been suggested as a means to decrease the risk of developing cataract. We aimed to investigate the hypothesis that an intervention with a Mediterranean diet (MedDiet) rather than a low-fat diet could decrease the incidence of cataract surgery in elderly subjects. Methods: We included 5802 men and women (age range: 55-80 years) from the Prevención con Dieta Mediterránea study (multicenter, parallel-group, randomized controlled clinical trial) who had not undergone cataract surgery. They were randomly assigned to one of three intervention groups: (1) a MedDiet enriched with extra-virgin olive oil (EVOO) (n = 1998); (2) a MedDiet enriched with nuts (n = 1914), and a control group recommended to follow a low-fat diet (n = 1890). The incidence of cataract surgery was recorded yearly during follow-up clinical evaluations. Primary analyses were performed on an intention-to-treat basis. Cox regression analyses were used to assess the relationship between the nutritional intervention and the incidence of cataract surgery. Results: During a follow-up period of 7.0 years (mean follow-up period: 5.7 years; median: 5.9 years), 559 subjects underwent cataract surgery. Two hundred and six participants from the MedDiet + EVOO group, 174 from the MedDiet + Nuts group, and 179 from the control group underwent cataract surgery. We did not observe a reduction in the incidence of cataract surgery in the MedDiet groups compared to the control group. The multivariable adjusted hazard ratios were 1.03 (95% confidence interval [CI]: 0.84-1.26, p = 0.79) for the control group versus the MedDiet + EVOO group and 1.06 (95% CI: 0.86-1.31, p = 0.58) for the control group versus the MedDiet + Nuts group. Conclusions: To our knowledge, this is the first large randomized trial assessing the role of a MedDiet on the incidence of cataract surgery. Our results showed that the incidence of cataract surgery was similar in the MedDiet with EVOO, MedDiet with nuts, and low-fat diet groups. Further studies are necessary to investigate whether a MedDiet could have a preventive role in cataract surgery. [ABSTRACT FROM AUTHOR]

Background: Obesity phenotypes with different metabolic status have been described previously. We analyzed metabolic phenotypes in obese coronary patients during a 5-year follow-up, and examined the factors influencing this evolution. Methods: The CORDIOPREV study is a randomized, long-term secondary prevention study with two healthy diets: Mediterranean and low-fat. All obese patients were classified as either metabolically healthy obese (MHO) or metabolically unhealthy obese (MUO). We evaluated the changes in the metabolic phenotypes and related variables after 5 years of dietary intervention. Results: Initially, 562 out of the 1002 CORDIOPREV patients were obese. After 5 years, 476 obese patients maintained their clinical and dietary visits; 71.8% of MHO patients changed to unhealthy phenotypes (MHO-Progressors), whereas the MHO patients who maintained healthy phenotypes (MHO-Non-Progressors) lost more in terms of their body mass index (BMI) and had a lower fatty liver index (FLI-score) (p < 0.05). Most of the MUO (92%) patients maintained unhealthy phenotypes (MUO-Non-Responders), but 8% became metabolically healthy (MUO-Responders) after a significant decrease in their BMI and FLI-score, with improvement in all metabolic criteria. No differences were found among dietary groups. Conclusions: A greater loss of weight and liver fat is associated with a lower progression of the MHO phenotype to unhealthy phenotypes. Likewise, a marked improvement in these parameters is associated with regression from MUO to healthy phenotypes. [ABSTRACT FROM AUTHOR]

Studies on the role of nutritional factors and physical activity (PA) in the pathogenesis of multiple sclerosis (MS) go back a long time. Despite the intrinsic difficulty of studying their positive or negative role in MS, the interest of researchers on these topics increased during the last few decades, since the role of diet has been investigated with the perspective of the association with disease-modifying drugs (DMD). The association of DMD, diets, and PA might have an additive effect in modifying disease severity. Among the various diets investigated (low-carbohydrate, gluten-free, Mediterranean, low-fat, fasting-mimicking, and Western diets) only low-carbohydrate, Mediterranean, and fast-mimicking diets have shown both in animal models and in humans a positive effect on MS course and in patient-reported outcomes (PROs). However, the Mediterranean diet is easier to be maintained compared to fast-mimicking and low-carbohydrate diets, which may lead to detrimental side effects requiring careful clinical monitoring. Conversely, the Western diet, which is characterized by a high intake of highly saturated fats and carbohydrates, may lead to the activation of pro-inflammatory immune pathways and is therefore not recommended. PA showed a positive effect both in animal models as well as on disease course and PROs in humans. Training with combined exercises is considered the more effective approach. [ABSTRACT FROM AUTHOR]

The Mediterranean diet (MD) prevents cardiovascular disease by different putative mechanisms, including modifications in the blood fatty acid (FA) profile. Polytherapy for secondary cardiovascular prevention might mask the effect of MD on the FA profile. This study was aimed to assess whether MD, in comparison with a low-fat diet (LFD), favorably modifies the blood FA profile in patients with coronary heart disease (CHD) on polytherapy. One hundred and twenty patients with a recent history of coronary stenting, randomized to MD or to LFD, completed 3 months of this open-label dietary intervention study. Diet Mediterranean-ness was evaluated using the Mediterranean Diet Adherence Screener (MeDAS) score. Both diets significantly reduced saturated FA (p < 0.01). Putative favorable changes in total n-3 FA (p = 0.03) and eicosapentaenoic acid plus docosahexaenoic acid (EPA + DHA; p = 0.04) were significantly larger with MD than with LFD. At 3 months, in the whole cohort, the MeDAS score correlated inversely with palmitic acid (R = −0.21, p = 0.02), and with palmitoleic acid (R = −0.32, p = 0.007), and positively with total n-3 FA (R = 0.19, p = 0.03), EPA (R = 0.28, p = 0.002), and EPA + DHA (R = 0.21, p = 0.02). In CHD patients on polytherapy, both MD and LFD shift FA blood composition towards a healthier profile, with a more favorable effect of MD on omega−3 levels. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is on the rise worldwide representing a public health issue. Its coexistence with obesity and other metabolic alterations is highly frequent. Therefore, current therapy interventions for NAFLD are mainly focused on progressive weight loss through modulation of overall calorie intake with or without specific macronutrient adjustments. Furthermore, other relevant nutritional interventions are built on food selection and time-restricted eating. Since every strategy might bring different results, choosing the optimal diet therapy for a patient is a complicated task, because NAFLD is a multifactorial complex disease. Importantly, some factors need to be considered, such as nutrition-based evidence in terms of hepatic morphophysiological improvements as well as adherence of the patient to the meal plan and adaptability in their cultural context. Thus, the purpose of this review is to explore and compare the subtleties and nuances of the most relevant clinical practice guidelines and the nutritional approaches for the management of NAFLD with a special attention to tangible outcomes and long-term adherence. [ABSTRACT FROM AUTHOR]

Type-2 diabetes mellitus (T2DM) has become a major health problem worldwide. T2DM risk can be reduced with healthy dietary interventions, but the precise molecular underpinnings behind this association are still incompletely understood. We recently discovered that the expression profile of the splicing machinery is associated with the risk of T2DM development. Thus, the aim of this work was to evaluate the influence of 3-year dietary intervention in the expression pattern of the splicing machinery components in peripheral blood mononuclear cells (PBMCs) from patients within the CORDIOPREV study. Expression of splicing machinery components was determined in PBMCs, at baseline and after 3 years of follow-up, from all patients who developed T2DM (Incident-T2DM, n = 107) and 108 randomly selected non-T2DM subjects, who were randomly enrolled in two healthy dietary patterns (Mediterranean or low-fat diets). Dietary intervention modulated the expression of key splicing machinery components (i.e., up-regulation of SPFQ/RMB45/RNU6, etc., down-regulation of RNU2/SRSF6) after three years, independently of the type of healthy diet. Some of these changes (SPFQ/RMB45/SRSF6) were associated with key clinical features and were differentially induced in Incident-T2DM patients and non-T2DM subjects. This study reveals that splicing machinery can be modulated by long-term dietary intervention, and could become a valuable tool to screen the progression of T2DM. [ABSTRACT FROM AUTHOR]

A high-fat diet (HFD) can easily induce obesity and change the gut microbiota and its metabolites. However, studies on the effects of high-fat diets on the host have drawn inconsistent results. In this study, the unexpected results showed that the refined HFD increased gut microbiota diversity and short-chain fatty acids (SCFAs), causing an increase in energy metabolism. Further analysis revealed these changes were caused by the different fiber content in these two diets. Male C57BL/6J mice (4–5 weeks old) were fed either HFD or refined low-fat diet (LFD) for 14 weeks. The metabolic rates, thermogenesis, gut microbiome, and intestinal SCFAs were tested. The HFD triggered obesity and disturbed glucose homeostasis. Mice fed HFD ingested more fiber than mice fed LFD (p < 0.0001), causing higher intestinal SCFA concentrations related to the increased abundances of specific bacteria in the HFD group. Also, the HFD increased metabolic heat and up-regulated thermogenesis genes uncoupling protein 1(Ucp-1), peroxisome proliferator-activated receptor-γ coactivator-1α (Pgc-1α) expression in the brown adipose tissue (BAT). It was revealed by 16S rRNA gene sequencing that the HFD increased gut microbial diversity, which enriched Desulfovibrionaceae, Rikenellaceae RC9 gut group, and Mucispirillum, meanwhile, reduced the abundance of Lactobacillus, Bifidobacterium, Akkermansia, Faecalibaculum, and Blautia. The predicted metabolic pathways indicated HFD increased the gene expression of non-absorbed carbohydrate metabolism pathways, as well as the risks of colonization of intestinal pathogens and inflammation. In conclusion, the HFD was obesogenic in male C57BL/6J mice, and increased fiber intake from the HFD drove an increase in gut microbiota diversity, SCFAs, and energy expenditure. Meanwhile, the differences in specific nutrient intake can dissociate broad changes in energy expenditure, gut microbiota, and its metabolites from obesity, raising doubts in the previous studies. Therefore, it is necessary to consider whether differences in specific nutrient intake will interfere with the results of the experiments. [ABSTRACT FROM AUTHOR]

Metabolic syndrome is a cluster of metabolic risk factors, characterized by abdominal obesity, dyslipidemia, low levels of high-density lipoprotein cholesterol (HDL-c), hypertension, and insulin resistance. Lifestyle modifications, especially dietary habits, are the main therapeutic strategy for the treatment and management of metabolic syndrome, but the most effective dietary pattern for its management has not been established. Specific dietary modifications, such as improving the quality of the foods or changing macronutrient distribution, showed beneficial effects on metabolic syndrome conditions and individual parameters. On comparing low-fat and restricted diets, the scientific evidence supports the use of the Mediterranean Dietary Approaches to Stop Hypertension (DASH) diet intervention as the new paradigm for metabolic syndrome prevention and treatment. The nutritional distribution and quality of these healthy diets allows health professionals to provide easy-to-follow dietary advice without the need for restricted diets. Nonetheless, energy-restricted dietary patterns and improvements in physical activity are crucial to improve the metabolic disturbances observed in metabolic syndrome patients. [ABSTRACT FROM AUTHOR]

Lifestyle modifications are the main support of nonalcoholic fatty liver disease (NAFLD) therapy. Weight loss is one of the primary goals in NAFLD, but the effects of different calorie-restricted diets remain unclear. Thus, we evaluated the effects of two calorie-restricted diets-the Mediterranean diet (Med diet) and low-fat diet-on liver status, cardiometabolic markers, and fatty acid profiles in patients with NAFLD. Twenty-four overweight/moderately obese men were randomly assigned to consume one of these diets. Lipid levels, glucose, insulin, liver enzymes, steatosis, and fatty acid profiles of serum and erythrocytes phospholipids were assessed. After 3 months, all participants had a significant weight loss (>9%), with improvements in waist circumference, body fat %, index of visceral adiposity (VAI), lipid accumulation product, fatty liver (FLI), and hepatic steatosis (HSI) index ( p < 0.001). Both diets significantly lowered triglycerides, total and LDL-cholesterol, liver enzymes, fasting glucose, insulin, and HOMA-IR index. Fatty acid profiles were enhanced after both diets, with a significantly decreased n -6/ n -3 ratio. Participants on the Med diet had higher levels of HDL-cholesterol and monounsaturated and n -3 docosahexaenoic acids in serum phospholipids and lower levels of saturated fatty acids, triglycerides, TG/HDL ratio, and FLI when compared to participants on the low-fat diet. Our results indicate that dietary patterns and calorie restriction represent central therapeutic issues in the improvement of obesity-related cardiometabolic alterations that are involved in the mechanism of hepatic steatosis. The Med diet may contribute to disease treatment even more than the low-fat diet since it leads to decreased saturated and increased monounsaturated and n -3 polyunsaturated fatty acid status and improved FLI in NAFLD patients.

Despite an ever-increasing burden of non-communicable diseases and overwhelming evidence that good nutrition improves outcomes it is difficult to know whether this evidence is reaching the general population. The purpose of this study was to investigate whether health professionals in Tairāwhiti have sufficient nutrition education for their roles in health education and promotion and whether nutrition beliefs held by health professionals were consistent with current literature. A particular interest was to enlist views on the harms, benefits, and possible barriers to following plant-based diets. A mixed-methods study involving health professionals completing a questionnaire and a subsequent focus group to collect data was used. Survey data were analysed using spreadsheet software, and thematic content analysis of focus group data was undertaken. Participants provided nutrition advice 2.4 times per day. Almost half of practitioners considered their nutrition knowledge to be inadequate, and most made poor use of references for provision of information. Plant-based diets were generally viewed as beneficial to health, improve quality of life, be filling, but were perceived as not as easy to follow. This study is in keeping with previous research that the health workforce would benefit from more formalised nutrition education and competencies to address common chronic disease. [ABSTRACT FROM AUTHOR]

Poor diet quality is the leading cause of death both in the United States and worldwide, and the prevalence of obesity is at an all-time high and is projected to significantly worsen. Results from an eight-week group program utilizing an ad-libitum whole-food plant-based dietary pattern, were reviewed. There were 79 participants, all self-referred from the community, including 24 (30.4%) who were already vegetarian or vegan at baseline. Seventy-eight participants (98.7%) completed the eight-week program. Among completers, those with higher BMI at baseline lost a larger percentage of their body weight (total body weight loss of 3.0 ± SD 2.1%, 5.8 ± 2.8%, and 6.4 ± 2.5% for participants who had baseline BMI in normal, overweight, and obese range, respectively). The average weight loss for all the completers was 5.5 ± 3.0 kg (p < 0.0001). Final blood pressure and plasma lipids were reduced compared to baseline (SBP decreased 7.1 ± 15.5 mmHg (p = 0.0002), DBP decreased 7.3 ± 10.9 mmHg (p < 0.0001), total cholesterol decreased 25.2 ± 24.7 mg/dL (p < 0.0001), LDL decreased 15.3 ± 21.1 mg/dL (p < 0.0001)). Twenty-one (26.9%) participants were able to decrease or stop at least one chronic medication compared to two (2.6%) participants who required an increased dose of a chronic medication. Participants who were already vegetarian or vegan at baseline experienced statistically significant weight loss and reductions in total and LDL cholesterol. There was a non-significant trend toward less weight loss in these participants compared to participants who were non-vegetarian at baseline. Reductions in total and LDL cholesterol were not significantly different when comparing vegetarian or vegan and non-vegetarian participants. A whole-food plant-based dietary intervention may provide significant short-term benefits for both non-vegetarian, vegetarian, and vegan individuals. [ABSTRACT FROM AUTHOR]

Obesity is associated with microvascular dysfunction. While low-fat diet improves cardiovascular risk, its contributions on microvascular function, independent of weight loss, is unknown. We tested the hypothesis that nitric oxide (NO)-dependent vasodilation in microvessels is improved by low-fat diets designed for weight loss (LFWL) compared to low-fat weight maintenance (LFWM) diet. Obese adults were randomly assigned to either a LFWL diet (n = 11) or LFWM diet (n = 10) for six weeks. Microvessels were obtained from gluteal subcutaneous fat biopsies before and after the intervention for vascular reactivity measurements to acetylcholine (Ach) and flow, with and without L-NAME or indomethacin. Vascular and serum NO and C-reactive protein (CRP) were also measured. LFWL diet increased flow-induced (FID) and ACh-induced dilation (AChID); an effect that was inhibited by L-NAME. Conversely, LFWM diet did not affect FID or AChID. Indomethacin improved FID and AChID in the baseline and this effect was minimized in response to both diets. Serum NO or CRP did not change in response to either diet. In conclusion, LFWL diet improves microvascular reactivity compared to LFWM diet and increased vascular NO contribution to the improved microvascular dilation. These data suggest that weight reduction on low fat diet is critical for microvascular health. [ABSTRACT FROM AUTHOR]

Background: This study aimed at assessing the effect of a low-fat diet (LFD) in obese mice lacking toll–like receptors (Tlr) and understanding the expression and regulation of microRNAs during weight reduction. Methods: C57BL/6, Tlr5−/−, Tlr2−/− and Tlr4−/− mice were used in this study. A group of mice were fed with a high-fat diet (HFD) (58% kcal) for 12 weeks to induce obesity (diet-induced obesity, DIO). Another group that had been fed with HFD for eight weeks (obese mice) were switched to a low-fat diet (LFD) (10.5% kcal) for the next four weeks to reduce their body weight. The control mice were fed with a standard AIN-76A diet for the entire 12 weeks. The body weight of the mice was measured weekly. At the end of the experiment, epididymal fat weight and adipocyte size were measured. The differentially expressed miRNAs in the fat tissue was determined by next-generation sequencing with real-time quantitative reverse transcription polymerase chain reaction (RT–qPCR). Target prediction and functional annotation of miRNAs were performed using miRSystem database. Results: Switching to LFD significantly reduced the body weight and epididymal fat mass in the HFD-fed C57BL/6 and Tlr5−/− mice but not in Tlr2−/− and Tlr4−/− mice. Weight reduction significantly decreased the size of adipocytes in C57BL/6 but not in the Tlr knockout mice. In Tlr2−/− and Tlr4−/− mice, feeding with HFD and the subsequent weight reduction resulted in an aberrant miRNA expression in the epididymal fat tissue unlike in C57BL/6 and Tlr5−/−. However, target prediction and functional annotation by miRSystem database revealed that all the top 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) database pathways of the dysregulated miRNAs during weight reduction in the C57BL/6 mice were also found in the regulated pathways of Tlr5−/−, Tlr2−/−, and Tlr4−/− strains. However, among these pathways, gene sets involved in arginine and proline metabolism and glutathione metabolism were mainly involved in the Tlr knockout mice but not in the C57BL/6 mice. Conclusions: In this study, we demonstrated that feeding of LFD leads to significant body weight reduction in C57BL/6 and Tlr5−/− mice, but not in Tlr2−/− and Tlr4−/− mice. Significant reduction in the size of adipocytes of epididymal fat was only found in C57BL/6, but not in Tlr5−/−, Tlr2−/−, and Tlr4−/− mice. The dysregulated miRNAs in Tlr2−/− and Tlr4−/− mice were different from those in C57BL/6 and Tlr5−/− strains. Among those miRNA-regulated pathways, arginine and proline metabolism as well as glutathione metabolism may have important roles in the Tlr knockout mice rather than in C57BL/6 mice. [ABSTRACT FROM AUTHOR]

The role of dietary fat has been long studied as a modifiable variable in the prevention and treatment of noncommunicable cardiometabolic disease. Once heavily promoted to the public, the low-fat diet has been demonstrated to be non-effective in preventing cardiometabolic disease, and an increasing body of literature has focused on the effects of a relatively higher-fat diet. More recent evidence suggests that a diet high in healthy fat, rich in unsaturated fatty acids, such as the Mediterranean dietary pattern, may, in fact, prevent the development of metabolic diseases such as type 2 diabetes mellitus, but also reduce cardiovascular events. This review will specifically focus on clinical trials which collected data on dietary fatty acid intake, and the association of these fatty acids over time with measured cardiometabolic health outcomes, specifically focusing on morbidity and mortality outcomes. We will also describe mechanistic studies investigating the role of dietary fatty acids on cardiovascular risk factors to describe the potential mechanisms of action through which unsaturated fatty acids may exert their beneficial effects. The state of current knowledge on the associations between dietary fatty acids and cardiometabolic morbidity and mortality outcomes will be summarized and directions for future work will be discussed. [ABSTRACT FROM AUTHOR]