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Adipose browning leads to increased energy expenditure and reduced adiposity and has, therefore, become an attractive therapeutic strategy for obesity. In this study, we elucidated the effect of green tea aqueous extract (GTAE) on the browning of inguinal white adipose tissue (Ing‐WAT) and brown adipose tissue (BAT) in high‐fat diet (HFD)‐fed mice. The main phytochemical components identified in GTAE through high‐performance liquid chromatography (HPLC) included (−)‐gallocatechin, (−)‐epigallocatechin, (−)‐catechin, (−)‐epigallocatechin‐3‐gallate, caffeine, (−)‐epicatechin, (−)‐gallocatechin gallate, and (−)‐epicatechin‐3‐gallate. Daily supplementation with 1% GTAE for 12 weeks markedly reduced bodyweight gain, systemic inflammation, oxidative stress, and improved insulin resistance. Additionally, histological analysis revealed that dietary supplementation with 1% GTAE reversed HFD‐induced adipocyte size and hepatic steatosis. These effects were associated with activation of browning in the Ing‐WAT and BAT, which mediate systemic metabolic dysfunction in HFD‐fed mice. Taken together, our data support the use of GTAE, a natural product, for the attenuation of obesity through the activation of fat browning., The present study found that mice fed a high‐fat diet showed significantly lower weight gain upon GTAE administration than their control counterparts. In addition, GTAE ameliorated the high‐fat diet‐induced hepatic steatosis, insulin resistance, and low‐systematic inflammatory. These effects were associated with browning activation in the Ing‐WAT and BAT.

Using mice as an animal model, we first demonstrated the significant proliferation of ARGs and the change of mobile genetic elements (MGEs) in high-fat diet induced obesity (DIO) mice, which the ermB and tnpA-03 genes mostly increased, illuminating that DIO could enrich the abundance of ARGs. Additionally, Lactobacillus sharply increased in the DIO mice and might contribute to the proliferation of ARGs and dramatical change of MGEs in the HFD groups. Finally, procrustes analysis showed the explanatory variables of the MGEs, the metabolites, and the microbial communities for the ARGs accounted for 94.3%, 53.4%, and 68.1%, respectively, and implying that MGEs might be the most direct factor affecting ARGs, and microbiota could be the main driver of the proliferation of ARGs in the DIO mice.

Background: Obesity, a metabolic disorder caused by an imbalance in energy intake and energy expenditure, is a major risk factor for chronic diseases such as type 2 diabetes, hypertension, cardiovascular heart diseases (CHD) and some types of cancer. This research was designed to investigate the effect of antioxidant rich- nutraceuticals in the management of high fat diet-induced obesity in rats. Method: Induction of obesity was achieved by feeding rats with a formulated high fat diet (HFD) for ten (10) weeks. Rats were subsequently group administered 250mg/kg body weight and 500mg/kg body weight of the nutraceutical respectively while apple cider vinegar of 5ml/kg body weight was administered to the standard group. Result: Supplementation showed significant (P

Circadian disruptions precede high-fat diet (HFD)-induced obesity (DIO). Deviation of the endogenous circadian rhythm period length (tau) from 24 hours correlates with mice inter-strain DIO under t...

Obesity is an important independent risk factor for type 2 diabetes, cardiovascular diseases, and many other chronic diseases. The objective of this study was to determine the role of adenosine deaminase acting on RNA 1 (ADAR1) in the development of obesity and insulin resistance. Wild-type (WT) and heterozygous ADAR1-deficient (Adar1(+/−)) mice were fed normal chow or a high-fat diet (HFD) for 12 wk. Adar1(+/−) mice fed with HFD exhibited a lean phenotype with reduced fat mass compared with WT controls, although no difference was found under chow diet conditions. Blood biochemical analysis and insulin tolerance test showed that Adar1(+/−) improved HFD-induced dyslipidemia and insulin resistance. Metabolic studies showed that food intake was decreased in Adar1(+/−) mice compared with the WT mice under HFD conditions. Paired feeding studies further demonstrated that Adar1(+/−) protected mice from HFD-induced obesity through decreased food intake. Furthermore, Adar1(+/−) restored the increased ghrelin expression in the stomach and the decreased serum peptide YY levels under HFD conditions. These data indicate that ADAR1 may contribute to diet-induced obesity, at least partially, through modulating the ghrelin and peptide YY expression and secretion. NEW & NOTEWORTHY This study identifies adenosine deaminase acting on RNA 1 as a novel factor promoting high-fat diet-induced obesity, at least partially, through modulating appetite-related genes ghrelin and PYY.

As per today’s modern world unhealthy and stressful life style and wrong eating habits have lead to a deadly condition which effects our healthy well being and becomes a cause for various disease which effects the longevity of life, yes it is nothing else than Obesity called as Sthoulya in Ayurved. Marich is responsible for destroying Visha, Jantu, Kapha, and Vata from body. It is useful in scraping Kapha from the body. Aim of the study is to evaluate the effect of Marich Churna in experimental model of high fat diet induced obesity. The experimental study was carried out for 42 days. In which for the first 21 days, the obesity was induced by creating high fat induced obesity experimental model of Wistar rats male, which was further treated for next 21 days with three different test drug dosage of Marich (A), of 90mg/kg., Marich (B) of 180mg/kg and Marich (C) of 270mg/kg were used. For obesity induction Vanaspati Ghee (Dalda) and coconut oil (Parachute) was used in which daily pellets were soaked overnight. The weight was recorded on weekly basis where as the blood samples were collected on 0, 21 and 42 days respectively. Standard Drug Atorvastatin was used. The blood samples were sent for histopathological results and the statistical analysis was done with Annova method. Obesity was induced till day 21 and again was reduced satisfactorily by Marich group (A) and group (C ) showed maximum satisfactory results with histopathological changes. Marich has anti-obesity potential. According to variation of dose the results have significant changes.

Numerous epidemiological studies have reported that moderate alcohol drinking has beneficial effects. However, few studies have focused on the beneficial effects of ethanol, the common component in alcoholic beverages. Here we fed the C57BL/6 mice with 3.5% v/v ethanol as drinking water substitute to investigate the effects of long-term low-dose ethanol intake in vivo. We evaluated the metabolic rate and mitochondrial function of the long-term low-dose ethanol-intake (LLE) mice, assessed the exercise ability of LLE mice, and fed the LLE mice with a high-fat diet to investigate the potential impact of ethanol on it. The LLE mice showed improved thermogenic activity, physical performance, and mitochondrial function, as well as resistance against the high-fat diet-induced obesity with elevated insulin sensitivity and subdued inflammation. Our results suggest that long-term low-dose ethanol intake can improve healthspan and resist high-fat diet-induced obesity in mice. It may provide new insight into understanding the protective effects of moderate alcohol drinking.

A high-fat diet (HFD) promotes oxidative stress, which contributes to the development of kidney dysfunction. We examined the protective effects of an ethanol extract of artichoke leaves (EEA) compa...

Trefoil Factor Family Member 2 (TFF2) belongs to TFF family peptides that includes TFF1, TFF2, TFF3. TFF2 is mainly known for its roles in the mucosal protection. In the context of obesity and high fat diet (HFD), Tff2 has been characterized as a HFD-induced gene. The knock-out of Tff2 in mice lead to the protection from HFD-induced obesity with a metabolic profile towards a negative energy balance. Such HFD-specific expression gives Tff2 a pattern worth exploring in biomedical research. Indeed, measuring TFF2/TFF2/Tff2 expression in biological samples following the ingestion of high-fat diet reflects the biological “responsiveness” to the lipids ingestion and would reflect the severity of obesity establishment afterwards. Such property could be explored for instance to screen animal models, evaluate the predisposition to HFD-induced obesity as well as in biomedical and clinical applications. Results might advance obesity research especially in terms of understanding lipid-induced signals, appetite control and adiposity storage.

Gut fungi is known to play many important roles in human health regulations. Herein, we investigated the anti-obesity efficacy of the antifungal antibiotics (amphotericin B, fluconazole and 5-fluorocytosine) in the high fat diet-fed (HFD) mice. Supplementation of amphotericin B or fluconazole in water effectively inhibited obesity and its related disorders, whereas 5-fluorocytosine exhibited little effects. The gut fungus Candida parapsilosis was identified as a key commensal fungus related to the diet-induced obesity by the culture-dependent method and the inoculation assay with C. parapsilosis in the fungi-free mice. In addition, the increase of free fatty acids in the gut due to the production of fungal lipases from C. parapsilosis was confirmed as one mechanism by which C. parapsilosis promotes obesity. The current study demonstrates the gut C. parapsilosis as a causal fungus for the development of diet-induced obesity in mice and highlights the therapeutic strategy targeting the gut fungi.

An upward trend in childhood obesity implies a great need to determine its effects, both immediate and long-term. Obesity is osteoprotective in adults, but we know very little about the effects of obesity on the growing skeleton, particularly its ability to adapt to load. The objective of this research is to assess bone mechanoadaptation in adolescent obese mice. Ten mice were fed a high-fat diet (HFD) from 4 to 16 weeks of age, while a control group of the same size received a normal diet (ND). At 14 weeks of age, right tibiae were cyclically loaded with a 12 N peak load for HFD mice and a 9 N peak load for ND mice three times a week for two weeks, resulting in equal peak strains of about 2500 microstrain. At 16 weeks of age, mice were sacrificed, and tibiae and gonadal fat pads were dissected. Fat pads were weighed as an obesity indicator, and tibiae were imaged with microCT to measure bone structure. The left tibiae (nonloaded) were subsequently decalcified, stained with osmium, and scanned to quantify marrow fat. Results showed that HFD mice had larger tibial cross-sectional areas compared to ND mice, as well as greater marrow adiposity. However, there was no significant difference in the amount of bone adaptation in the cortical or trabecular bone between the two groups. This indicates that the bones of HFD and ND mice adapt equally well to loading. ispartof: JOURNAL OF BIOMECHANICS vol:124 ispartof: location:United States status: published

Long-chain acyl-CoA synthetases (ACSL) are the enzymes that convert long-chain fatty acids to long-chain fatty acyl-CoAs that are utilized for various cellular processes, including triglyceride synthesis, energy metabolism, sphingolipid formation, and modification of lipids and proteins. Among five common isotypes (ACSL1, 3, 4, 5, and 6), ACSL1 is the predominant isotype in adipose tissue and essential for fatty acid oxidation during the cold adaption in brown adipose tissue. However, it is unknown whether ACSL1 is involved in brown adipocyte differentiation. Since the smooth muscle-like cells (mural cells) are the progenitors of brown adipocytes, we hypothesize that the ACSL1 in smooth muscle cells contributes to brown adipocyte differentiation and energy metabolism. We generated a smooth muscle-specific ACSL1 knockout mouse (ACSL1SM-/-) by breeding SM22α-cre mouse with ACSL1flox/flox mouse. ACSL1 deficiency in smooth muscle cells protected from high-fat diet (HFD)-induced obesity without changes in food intake and physical activity. Furthermore, HFD-fed ACSL1flox/flox mice were more glucose tolerant and insulin sensitive compared to HFD-fed wild-type mice. We also observed that cold adaptation, thermogenesis, was significantly impaired in ACSL1SM-/- mice. We isolated stromal vascular cells (SVCs) from inguinal and brown adipose tissues and then subjected them to adipocyte differentiation. We found that the adipocyte differentiation was impaired, and the expression of UCP1 was significantly reduced in the absence of ACSL1. These results suggest that ACSL1 in smooth muscle cells contributes to energy metabolism and glucose homeostasis by regulation of brown fat differentiation. Disclosure G. Ren: None. M. Young: None. J. Kim: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (P30DK079626); National Heart, Lung, and Blood Institute (HL128695); National Institute on Aging (AG058078)

Background and Objectives: The purpose of this research was to determine effects of vitamin D supplementation during a course of endurance training on anthropometrical parameters of Wistar rats exposed to a high-fat diet. Methods: In this experimental study, 38 Wistar rats aged 5-6 weeks were assigned to five groups: 1. Control with normal diet (n=5), 2. Control with high-fat diet (n=5), 3. High-fat diet and vitamin D supplementation (n=10), 4. High-fat diet and endurance training (n=10), and 5. High-fat diet, endurance training and vitamin D supplementation (n=10). The animals were subjected to a high-fat diet (40%) for 13 weeks, followed by 12 weeks of exercise and vitamin D supplementation. Results: Weight (P=0.02), BMI (P=0.001), Lee index (P=0.01) and energy efficiency (P=0.001) differed significantly between groups 1 and 2. Feed efficiency (P=0.03) and energy efficiency (P=0.01) of groups 2, 3 and 4 were significantly different from that of the control group. Conclusion: The results of the present study indicate that endurance training and vitamin D supplementation could significantly decrease some anthropometric indices. Keywords: Endurance Training, Vitamin D, High Fat Diet, Anthropometric Indices.

Obesity is caused by an energy imbalance between food intake and energy expenditure, and has detrimental effects on human health. Platycodon (Platycodon grandiflorum) widely grows in Korea...

Brassicaceae contain bioactive compounds with potential positive effects on metabolic syndrome. Here, we evaluated the eventual anti-obesity properties of an ethanolic broccoli extract (BE), selected by a tested ability to reduce Caenorhabditis elegans fat content. Two doses (14 and 140 mg/kg animal) of BE were evaluated in a diet-induced obesity (DIO) Wistar rat model. After 10 weeks of BE supplementation, animals exhibited reduced body weight gain and food efficiency, decreased atherogenic index of plasma and improved glucose tolerance in comparison with non-supplemented rats. BE also reduced the retroperitoneal fat mass and adipocyte size, all associated to down-regulation of Cebpa, Srebp1, Fasn and Adipoq expression in adipocytes. Finally, BE significantly decreased liver steatosis, accompanied by the up-regulation of Acot8 and Acox1, and the down-regulation of Fasn, Fatp4 and Srebf1 expression in hepatocytes. Our data provides new knowledge about the potential role of broccoli components in the prevention of metabolic syndrome.

Objectives The goal of this study was to evaluate the modulatory effect of chitosan oligosaccharide-nisin conjugate (CON-C) on intestinal microbiota of human flora-associated (HFA) mice and also reveal its effect towards the high-fat diet (HFD)-induced obesity. Both Chitosan oligosaccharides and nisin showed great potential in modulating the intestinal microbiota, so it is worth to explore whether the modulation effect of chitosan oligosaccharide could be improved by covalently binding with nisin. Materials and Methods CON-C was prepared by heating the mixed solution of chitosan oligosaccharide and nisin at 80°C and pH 2.0 for 24h. The structure of CON-C were analyzed by Fourier transform-infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The CON-C’s anti-obesity effect and modulatory effect toward intestinal microbiota were analyzed using human flora-associated (HFA) mice model. Results CON-C could alleviated HFD-induced gut dysbiosis, by significantly decreasing the numbers of Bifidobacterium and Lactobacillus/Enterococcus spp., and increasing the numbers of Bacteroides–Prevotella and Clostridium groups. CON-C could also enriched the most differentially expressed genes through KEGG pathways of biosynthesis of amino acids, two-component system, and ATP binding cassette (ABC) transporters. Conclusions The improved therapeutic effect of CON-C against HFD-induced obesity has been approved, and hence, CON-C has a great potential to be utilized as a functional food ingredient in reducing body weight.

Aim To characterize gingival metabolome in high-fat diet (HFD)-induced obesity in mice with/without periodontitis. Methods HFD-induced obesity mouse model was established by 16-week feeding, and a lean control group was fed with low-fat diet (n = 21/group). Both models were induced for periodontitis on the left sides by molar ligation for 10 days, whereas the right sides were used as controls. Gingival metabolome and arginine metabolism were analysed by non-targeted/targeted liquid chromatography-mass spectrometry. Results Of 2247 reference features, presence of periodontitis altered 165 in lean versus 885 in HFD mice; and HFD altered 525 in absence versus 1435 in presence of periodontitis. Compared with healthy condition, periodontitis and HFD had distinct effects on gingival metabolome. Metabolomic impacts of periodontitis were generally greater in HFD mice versus lean controls. K-medoids clustering showed that HFD amplified the impacts of periodontitis on gingival metabolome in both intensity and extensity. Ten metabolic pathways were enriched, including 2 specific to periodontitis, 5 specific to HFD and 3 shared ones. Targeted validation on arginine metabolism confirmed the additive effects between HFD and periodontitis. Conclusion The obese population consuming excessive HFD display amplified metabolic response to periodontitis, presenting a metabolic susceptibility to exacerbated periodontal destruction.

Background: Dietary fat absorption involves the re esterification of digested triacylglycerol in the enterocytes, it is a biological process catalyzed by monoacylglycerol O acyltransferase 2 (MOGAT2, aka MGAT2), which is highly expressed in the small intestine. A previous study showed that the loss of the Mogat2 gene can prevent high fat diet induced obesity in mice. Obesity is associated with an increased risk of several types of cancer including postmenopausal breast cancer.Methods: We collected 147 patients with triple negative breast adenocarcinoma to explore the relationship between the expression of MOGAT2 and patient overall survival. And we generated a Mogat2 deficient mouse mammary tumor model by crossing Mogat2 deficient mice with MMTV PyMT mice to examine the effect of losing MOGAT2 in vivo. Results: Our founding suggest that obesity was induced by a relatively high fat diet (37% of calories from fat) in the mice with or without Mogat2 knockout. Mammary tumor development was deteriorated by a relatively high fat diet regardless of Mogat2 deficiency. As a compensation mechanism, upregulation of diacylglycerol O acyltransferases 1 and 2 (Dgat1 and Dgat2) in the Mogat2 deficient mice was found. Conclusions: Elevated expression of MOGAT2 in triple negative breast adenocarcinoma predicts poorer patient overall survival. With the compensation of Dgat1 and Dgat2, Mogat2 deficiency alone cannot prevent fat diet induced obesity, nor prevent mammary tumor development in a mouse model.

Background: Obesity is associated with many adverse effects on female fertility. Obese women are more likely to have ovulatory dysfunction due to dysregulation of the hypothalamic-pituitary-ovarian axis. However, ovarian function in obese women during early pregnancy still needs further assessment. Methods: Obesity was induced in C57BL6/J mice using high-fat diets (HFD) for 12 weeks; In vitro high-fat model was established with KGN cells treated with Oleate acid and Palmitic acid. Ovarian morphology of obese mice in early pregnancy was assessed by Hematoxylin and Eosin staining and its function was assessed using ELISA, Western blotting and Immunohistochemistry. The Oil Red O staining and Transmission electron microscopy were used to detect fatty acid accumulation and specific markers relating to ovarian functional mechanism were assessed by Real time PCR, Western blotting, Lactate detection, ATP detection, Biochemical analyses and ELISA.Results: The results of this study showed that during early pregnancy, the number of corpus luteum, serum estradiol and progesterone levels, and the expression of genes CYP19A1, CYP11A1 and StAR, which are related to steroid biosynthesis, were significantly increased in HFD female mice. HFD-fed mice also showed a significant increase in ovarian lipid accumulation on day 7 of pregnancy. Genes involved in fatty acid synthesis (Acsl4 and Elovl5) and fatty acid uptake and transport (Slc27a4), together with the β-oxidation rate-limiting enzyme (Cpt1a) were significantly upregulated in HFD-fed mice. Specifically, there was abnormal elevation of ATP level and aberrant expression of tricarboxylic acid cycle (TCA) and electron transport chain related genes in the ovary of HFD pregnant mice. Treatment of KGN cells with etomoxir targeting β-oxidation of fatty acid, showed decrease tricarboxylic acid cycle and electron transport chain. The elevated ATP level and the increased estradiol and progesterone levels were reversed. Conclusions: This study indicated that during early pregnancy, high-fat diet and induced-obesity increased fatty acid β-oxidation, which in turn increase the tricarboxylic acid cycle and the electron transport chain, and consequently increases ATP production and ovarian dysfunction.

Background According to epidemiologic studies, it was found that people living in high altitude areas have a lower prevalence of obesity and diabetes, and the main environmental differences between high altitude areas and plain areas are temperature and oxygen concentration. In this study, we investigated the effect of chronic transient hypoxia on obesity and fatty liver caused by high-fat diet in mice. Methods Put the mice under 10% oxygen concentration for 1 hour every day, this method is different from high altitude hypoxia and will not cause a series of acute altitude sicknesses. Intraperitoneal injection of epinephrine or propranolol was employed to examine the effect of chronic transient hypoxia on HFD-induced obesity, hyperglycemia and hepatic lipid accumulation. Results It showed that chronic transient hypoxia environment reduces the weight of mice and improve glucose tolerance, reduce the fat content of mice and alleviate fatty liver, reduces liver fat synthesis, promotes the expression M2 phenotype of macrophage genes in liver and thermogenic genes in brown fat. Furthermore, we showed that blocking the rise of epinephrine will compromise the chronic transient hypoxia environment beneficial ability to obesity and fatty liver, diminished expression of the liver AMPK phosphorylation and CD206. Conclusions These results suggest that chronic transient hypoxia activation of AMPK, induction of M2 type macrophage marker CD206 expression in the liver leads to significant weight loss and remission the severity of fatty liver through the adrenergic system.

Background and Objective:Beverages containing caffeine have an anti-obesity function. Reduction of visceral adipose tissue (VAT) inflammation is considered an important strategy to ameliorate obesity compilations such as insulin resistance. This study aimed to investigate the effect of 8-week caffeine supplementation on the messenger RNA (mRNA) expression of fetuin-A (FetA) in the liver and nuclear factorkappa B (Nf-κb) and toll-like receptor 4 (Tlr4) in the VAT of rats with a high-fat diet (HFD). Methods:A total of 40 male Wistar rats were randomly divided into control, caffeine, HFD, and HFD+caffeine supplement groups. After 2 weeks of acclimatization, the rats were randomly fed with HFD (46% fat) and a normal diet (5% fat) for 8 weeks. The rats in the caffeine groups were gavaged with 6 mg of the caffeine solution per kg of body weight. FetA mRNA of the liver, Nf-κb, and Tlr4 mRNA of VAT were determined using real-time polymerase chain reaction (PCR). Results:The results indicated that FetA mRNA expression and weight gain in HFD+caffeine were significantly reduced compared to the other groups. Nf-κb mRNA expression was significantly higher in the HFD group than in the caffeine groups. No statistically significant differences were found in Tlr4 mRNA expression between the groups. Conclusion:These findings suggest that consuming caffeine can prevent HFD-induced liver and adipose tissue (AT) inflammation. Keywords:High-fat diet,Caffeine,Adipose tissue,Inflammation,Fetuin-A,Toll-like receptor 4,Nuclear factor kappa B

Sargassum serratifolium (C.Agardh) C.Agardh, a marine brown alga, has been consumed as food and traditional medicine in Asia. A previous study showed that the meroterpenoid-rich fraction of an ethanolic extract of Sargassum serratifolium (MES) induced adipose tissue browning and suppressed diet-induced obesity and metabolic syndrome. Sargahydroquinoic acid (SHQA) is a major component in MES. However, it is unclear whether SHQA can regulate energy homeostasis through the central nervous system. To figure it out, SHQA was administrated through the third ventricle of the hypothalamus in high-fat diet-fed C57BL/6 mice and investigated its effects on energy homeostasis. Bath application of SHQA increases the intrinsic neuronal excitability of hypothalamic ARC neurons in acutely prepared brain slices. Thus, we further tested its effect on energy balance. Chronic administration of SHQA into the brain reduced bodyweight without a change in food intake and improved metabolic syndrome-related phenotypes. Cold experiments and biochemical analyses indicate that SHQA elevates thermogenic signaling pathways evidenced by an increase in body temperature and UCP1 signaling in white and brown adipose tissues. As partial mechanisms, SHQA significantly elevated mRNA levels of genes associated with sympathetic outflow and GABA signaling pathways. Our data indicate that hypothalamic injection of SHQA elevates peripheral thermogenic signaling and ameliorates diet-induced obesity.

Introduction: Sedentary lifestyle and excessive calorie intake are risk factors for CVD. We have demonstrated the cardioprotective effect of exercise in aged mice and the critical role of visceral adiposity and its profibrotic secretome in increasing cardiovascular risks in obesity and aging. The association between exercise, lowered plasma leptin and reduced inflammatory leukocytes has been recently shown in patients with atherosclerosis. It remains unclear whether elevated plasma leptin can preserve or alter cardiovascular function in obesity. Methods: We analyzed the effect of high fat diet (HFD) in C57BL/6J male mice on the heart in terms of function, structure, histology and key molecular markers. Two interventions were used: 1) active fat mass loss via exercise (daily swimming) during HFD; 2) passive fat mass loss via surgical removal of the visceral adipose tissue (VAT lipectomy) followed by HFD. Results: HFD increased body weight and adiposity, leading to higher plasma leptin, glucose and insulin levels, compared to control diet (CD) mice. HFD impaired left ventricle (LV) structure (hypertrophy, interstitial fibrosis) and cardiac function (echocardiography, in vivo hemodynamics). Atria of HFD mice had enhanced pro-inflammatory protein production. Exercise reduced circulating leptin levels in HFD mice by 50%, in line with fat mass loss. In contrast, lipectomy reduced visceral fat mass, but body weight, adiposity and plasma leptin did not change. Both exercise and VAT lipectomy improved cardiac contractility, reversed collagen deposition and oxidative stress in HFD mice. Both interventions downregulated LV pro-inflammatory markers. We proved the role of leptin in cardiac remodeling in vitro by incubating primary cardiac fibroblasts with hyperleptinemic plasma from HFD mice. Remarkably, plasma from HFD-EX (exercise) suppressed the fibro-proliferative and pro-inflammatory responses of cardiac fibroblasts. Conclusions: Leptin directly contribute to cardiac fibrosis in obesity via activation and proliferation of cardiac fibroblasts. Understanding how leptin signals to the heart might have implications in a wide range of CVD, potentially helping early stratification and personalized care.

Caffeic acid (CFA), a natural polyphenolic compound which exists in coffee, fruits and certain traditional Chinese medicine, is one promising anti-obesity agent with a variety of pharmacological activities. The objective of the current study was to determine the mechanism of anti-obesity effect of CFA, and the relationship between its anti-obesity effect and gut microbiota change in high fat diet induced obese (DIO) mice. The DIO mice were administrated CFA by daily gavage at 50 mg/kg body weight for 12 weeks. The results showed that CFA significantly ameliorated high fat diet induced obesity. Specifically CFA reduced body weight and fat accumulation, improved lipid profile and increased energy expenditure in DIO mice. Moreover, CFA restored gut microbiota imbalance and increased the abundance of anti-obesity related bacteria and butyrate-producing bacteria in DIO mice. We conclude that CFA is effective to reduce metabolic risks possibly by regulating gut microbiota.

Obesity is a health problem that has been associated with neuroinflammation, decreased cognitive functions and development of neurodegenerative diseases. Parkinson's disease (PD) is a chronic neurodegenerative condition characterized by motor and non-motor abnormalities, increased brain inflammation

Background Infections caused by pathogens carrying antibiotic resistance genes (ARGs) are triggering a global health crisis. Human gut microbiota is an important reservoir of ARGs, which can not only be exchanged inside the symbiotic microbiota, but can also be horizontally transferred to opportunistic pathogens. A dysbiotic gut microbiota has been associated with obesity and other metabolic disorders, which has also been described as the most unneglected global health problem. Many studies have focused on the effects of antibiotics and other exogenous chemical on the fate of ARGs, but little is known about the effect of obesity induced dysbiotic gut microbiota on the fate of ARGs. Results This study addressed the significant proliferation of ARGs and the dramatical change of mobile genetic elements (MGEs) in high-fat diet induced obesity (DIO) mice, which the ermB and tnpA-03 genes mostly increased, demonstrating that DIO alone could enrich the abundance of ARGs. A clear increase of serine and tyrosine in the feces showed a significant positive correlation with the dominant genes of DIO groups (ermB and tnpA-03), suggesting that serine and tyrosine might enhance DNA transposition (tnpA-03) by nucleophilic attacking a phosphorus atom of a backbone phosphate group and ultimately significantly amplified the ARGs. Additionally, ermB has been frequently found in obesity-associated Lactobacillus, which might contribute to the sharp increase of ARGs and dramatical change of MGEs in the DIO mice. Finally, procrustes analysis showed the explanatory variables of the MGEs, the metabolites, and the microbial communities for the ARGs accounted for 94.3%, 53.4%, and 68.1%, respectively. Conclusion This study demonstrated that DIO significantly enhanced the abundance of ARGs and dramatically changed MGEs in mouse gut microbiota. MGEs were the most direct factor affecting ARGs, and microbiota were the main driver of the proliferation of ARGs in the DIO mice.

Female obesity is associated with menstrual dysfunction leading to anovulation and infertility. It has recently been reported obesity-induced infertility is involved in the dysfunction of a kisspeptin neuron, a key player in reproduction via direct stimulation of gonadotropin releasing hormone (GnRH) and subsequent gonadotropin release in mammalian species. Previous studies reported that obesity due to high-fat diet (HFD) for 8 months induced a disruption in estrous cyclicity, caused by a decrease in Kiss1 (coding kisspeptin) expression in the hypothalamic arcuate nucleus (ARC) in female rodents. Here we showed the effects of shorter-term (4 months) HFD on pulsatile LH secretion and hypothalamic Kiss1 expression to show pathogenic mechanism underlying obesity-induced infertility. Female Wistar-Imamichi strain rats (7 weeks old) fed on either a standard diet (10% calories from fat) or a high-fat diet (45% calories from fat) for 4 months. Estrous cyclicity and body weight were monitored regularly. All animals were implanted with a jugular catheter and collected blood samples to analyze pulsatile LH secretion, after a week of the ovariectomy with low-dose replacement estradiol to negate influence of changes in ovarian steroid levels and mimic diestrous levels of plasma estrogen. On the next day of the blood sampling, rats were perfused with 0.05 M PBS followed by 4% paraformaldehyde and their brains were collected for in situ hybridization of Kiss1 and Gnrh1. The HFD-fed rats showed progressive increases in body weight, along with hyperphagia and adipose tissue accumulation, compared with control animals. Fifty-eight percent of the HFD-fed rats exhibited irregular estrous cycles, whereas remaining HFD-fed rats showed regular cycles. Two out of 7 rats showing HFD-induced irregular estrous cycles exhibited profound suppression of the LH pulse frequency and the number of Kiss1-expressing cells in the ARC, whereas remaining HFD-fed rats showed normal LH pulses and ARC Kiss1 expressions. The number of Kiss1-expressing cells in the ARC had close positive correlation with LH pulse frequency (R2=0.6872, P

Lipotoxicity is defined as deposition of excess fat associated with an inflammatory response. Metabolomic analysis of fatty acids (FAs) can be a marker of silent inflammation. ω3-Enriched diet, celecoxib, and safranal may have a protective anti-inflammatory role. In this work, total FAs extracted from red blood cells and arachidonic acid-to-eicosapentaenoic acid (AA-to-EPA) ratios were assessed using GC-MS assay in single-ion monitoring mode. The study was conducted on 64 male rats divided into eight groups: I, controls; II, rats received high-fat diet (HFD), III, rats received ω-6-enriched HFD; IV, rats received ω-3-enriched HFD; V, rats received celecoxib with HFD; VI, rats received safranal with HFD; VII and VIII, rats received celecoxib and safranal with ω-3 HFD, respectively. GC-MS Gas chromatography Mass spectrometry was performed for analysis of fatty acid methyl ester. Enzyme-linked immunosorbent assay was used to analyze serum interleukin-6 (IL-6) and transforming growth factor-beta 1 (TGF-β1) concentrations. A statistically significant decrease of AA-to-EPA ratio was observed in group VII when compared with the groups receiving HFDs. This group also showed the lowest serum IL-6 level and highest TGF-β1 level. In conclusion, ω3-enriched diet along with drugs (e.g. celecoxib) and herbal medications (e.g. safranal) may have an anti-inflammatory effect in lipotoxicity. GC-MS with single-ion monitoring is valid for the analysis of FAs.

Green tea could reportedly modify gut microbiota and benefit on High-Fat-Diet (HFD) induced obesity. However, most of the studies usually gave green tea (GT) to animals while feeding them HFD. When thin or obese mice, drink GT continuously or only for a period of time, what kind of benefit will them get, is still need to evaluate. In this study, we found that preventive GT consumption by lean mice could prevent HFD-induced-obesity event after stop drinking GT, while the mice with pre-existing obesity couldn’t get such benefit. Gut microbiota structure analysis indicated that the anti-obesity effect by GT consumption always accompanied with microbiota structure modification. We hypothesized that this difference depended upon the status of gut microbiota. Therefore, to gain the persistently protective effect from GT, the precondition is drinking GT before getting fat; otherwise, GT could only slowdown the weight gain of the pre-obese mice by continuously consumption.

20-Hydroxyeicosatetraenoic acid (20-HETE) has been shown to positively correlate with body mass index, hyperglycemia, and plasma insulin levels. This study seeks to identify a causal relationship between 20-HETE and obesity-driven insulin resistance. Cyp4a14−/− male mice, a model of 20-HETE overproduction, were fed a regular or high-fat diet (HFD) for 15 wk. 20-SOLA [2,5,8,11,14,17-hexaoxanonadecan-19-yl 20-hydroxyeicosa-6( Z),15( Z)-dienoate], a 20-HETE antagonist, was administered from week 0 or week 7 of HFD. HFD-fed mice gained significant weight (16.7 ± 3.2 vs. 3.8 ± 0.35 g, P < 0.05) and developed hyperglycemia (157 ± 3 vs. 121 ± 7 mg/dl, P < 0.05) and hyperinsulinemia (2.3 ± 0.4 vs. 0.5 ± 0.1 ng/ml, P < 0.05) compared with regular diet-fed mice. 20-SOLA attenuated HFD-induced weight gain (9.4 ± 1 vs. 16.7 ± 3 g, P < 0.05) and normalized the hyperglycemia (157 ± 7 vs. 102 ± 5 mg/dl, P < 0.05) and hyperinsulinemia (1.1 ± 0.1 vs. 2.3 ± 0.4 ng/ml, P < 0.05). The impaired glucose homeostasis and insulin resistance in HFD-fed mice evidenced by reduced insulin and glucose tolerance were also ameliorated by 20-SOLA. Circulatory and adipose tissue 20-HETE levels significantly increased in HFD-fed mice correlating with impaired insulin signaling, including reduction in insulin receptor tyrosine (Y972) phosphorylation and increased serine (S307) phosphorylation of the insulin receptor substrate-1 (IRS-1). 20-SOLA treatments prevented changes in insulin signaling. These findings indicate that 20-HETE contributes to HFD-induced obesity, insulin resistance, and impaired insulin signaling.

Obesity usually induces overactive bladder (OAB) associated with detrusor overactivity, which is related to increased contractility of the detrusor smooth muscle (DSM). Small-conductance Ca2+-activated K+ (SK) channels play a constitutive role in the regulation of DSM contractility. However, the role of SK channels in the DSM changes in obesity-related OAB is still unknown. Here, we tested the hypothesis that obesity-related OAB is associated with reduced expression and activity of SK channels in DSM and that SK channels activation is a potential treatment for OAB. Female Sprague–Dawley rats were fed a normal diet (ND) or a high-fat diet (HFD) and weighed after 12 weeks. Urodynamic studies, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and isometric tension recording were performed. Increased average body weights and urodynamically demonstrated OAB were observed in HFD rats. qRT-PCR experiments revealed a decrease in the mRNA expression level of SK channel in DSM tissue of the HFD rats. Isometric tension recordings indicated an attenuated relaxation effect of NS309 on the spontaneous phasic and electrical field stimulation-induced contractions that occurred via SK channel activation in HFD DSM strips. Reduced expression and activity of SK channels in the DSM contribute to obesity-related OAB, indicating that SK channels are a potential therapeutic target for OAB.

The study investigated how an extract of Sporidiobolus pararoseus (S.p.) affects lipid metabolism in Kunming mice that were obese as a result of being fed a high-fat diet; the control group were administered Max EPA fish oil. Ten mice were randomly selected from a pool of 60 mice for the control group and the remaining 50 mice were fed with a high-fat diet to establish a dyslipidemia model. After 4 weeks, these 50 mice were randomly distributed among 5 groups: high-fat model group; Max EPA group; and 3 groups of mice fed different doses of S.p. extract (low dose, medium dose, and high dose). After 8 weeks, the mice were sacrificed and the relevant parameters were measured. Compared with the high-fat model group, the group administered the high dose of S.p. extract showed significantly decreased body mass and serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, and increased levels of high-density lipoprotein cholesterol. The results from RT-PCR showed that the mRNA expression of sterol regulatory element-binding protein 1c, fatty acid synthesis enzyme, and acetyl-CoA carboxylase was lower in the groups supplemented with S.p. extract than in the high-fat model group, whereas the expression of carnitine palmitoyltransferase 1 was higher in the group supplemented with S.p. extract than in the high-fat model group. Our results suggest that taking S.p. extract could benefit patients with dyslipidemia. Therefore, S.p. extract should be developed as a dietary supplement to improve lipid metabolism in obese people.

Aims Obesity induce low-grade inflammation and elicit insulin resistance (IR), exercise training accompanied by a low-fat diet has been prescribed as part of the treatment for managing obesity and IR. The purpose of this study is to evaluate the effect of eccentric exercise accompanied by a low-fat diet on glycolipid metabolism, exercise capacity, and macrophage polarization in obesity-induced IR mice. Materials and methods Mice were fed with 60% high fat diet (HFD) for 12 weeks and subsequently treated with eccentric exercise or/and dietary restriction for 8 weeks. Related biochemical index were examined both before and during intervention to evaluate the ability of glycolipid metabolism. Exercise capacity was measured to verify the results of biochemical index. At 12 weeks and 12 + 8 weeks, infiltration was observed by H&E staining in adipose tissue, and macrophage polarization was detected by Immunofluorescence staining and ELISA. Key finding 1) obesity-induced IR model was established by HFD fed for 12 weeks accompanied by impaired exercise ability and increased M1 macrophage, 2) eccentric exercise accompanied by a low-fat diet markedly rescued obesity-induced IR and improved exercise capacity, 3) eccentric exercise accompanied by a low-fat diet markedly inhibited M1 macrophage polarization and activated M2 macrophage. Significance Eccentric exercise accompanied by a low-fat diet rescued obesity-induced IR and improved exercise capacity, which were associated with the inhibition of M1 macrophage polarization and the activation of M2 macrophage. These indicate that macrophage polarization provides the potential target of intervention for inflammation and IR in obesity.

Altered regulation of vitamin D metabolites, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D (1,25[OH]2D), was observed in high-fat diet (HFD)-induced obesity. We hypothesized that these HFD-induced changes in vitamin D metabolism would be reversed by decreasing fat mass through dietary intervention. Four-week-old C57BL/6J mice were assigned to 1 of 3 experimental diet groups: (1) the LL group was fed a control diet for 31 weeks, (2) the HH group was fed an HFD for 31 weeks, and (3) the HL group was fed HFD for 15 weeks then switched to the control diet for the remaining 16 weeks. The fat mass of the HL group decreased by 15% from the 14th to the 30th week. Serum 1,25(OH)2D level was significantly higher in the HH group than the LL group, whereas that of the HL group was intermediate to the 2 groups. Serum parathyroid hormone and renal 1-hydroxylase (Cyp27b1) mRNA levels, which are known to stimulate renal 1,25(OH)2D production, were significantly higher in the HH group than the LL group. After losing fat mass, the HL group had significantly lower renal Cyp27b1 mRNA levels than the HH group. No differences were found in serum 25-hydroxyvitamin D levels and mRNA levels of hepatic 25-hydroxylases. In adipose tissue, mRNA levels of 25-hydroxylase and vitamin D receptor were elevated in parallel to the adiposity. In conclusion, serum 1,25(OH)2D levels were closely associated with body adiposity, and reducing fat mass by changing to a lower-fat diet can reverse this obesity-associated increase in circulating 1,25(OH)2D levels.

In this study, we evaluated the ameliorative potential of Cucurbita maxima seeds oil (CSO (100 mg/kg body weight)) supplementation to high fat diet (HFD)-induced obese rats for 30 days on the changes in body weight, markers of lipid metabolism such as LDL, HDL, triglycerides, total cholesterol, adiponectin, leptin, amylase, and lipase. We also investigated the effects of CSO on the changes of lipid metabolic enzymes such as fatty-acid synthase, acetyl CoA carboxylase, carnitine palmitoyl transferase-1, HMG CoA reductase, and inflammatory markers (TNF-α and IL-6). Administration of CSO revealed significant diminution in body weight gain, altered the activity, expressions of lipid marker enzymes and inflammatory markers. It demonstrated that CSO had considerably altered these parameters when evaluated with HFD control rats. In conclusion, this study suggested that CSO might ameliorate the HFD-induced obesity by altering the enzymes and mRNA expressions important to lipid metabolism.

We aimed to clarify the key factor determining the effect of beta blocker attenuating high fat diet- induced obesity and bone loss. Six-week-old C57BL/6 male mice were assigned to groups reflecting different relative onset of obesity and beta blocker administration, different diet (control vs. high fat), and treatment (vehicle vs. beta blocker: propranolol). Mice in Group 1 were fed a control diet (CON) or high fat diet (HIGH) with vehicle or propranolol for 12 weeks. Mice in Group 2 were fed a CON or HIGH without pharmaceutical treatment for the first 12 weeks, followed by another 12 weeks of treatment with vehicle or propranolol. Mice in Group 3 were fed a CON without pharmaceutical treatment for the first 12 weeks, followed by stratification into diet-based subgroups and another 12 weeks of treatment with vehicle or propranolol. Propranolol attenuated the HIGH-induced increase in body weight/fat mass in Group 1 mice and in Group 3 mice, but not in Group 2 mice. Propranolol mitigated HIGH-induced reduction in femoral trabecular bone mineral density and bone architecture deterioration in Group 1 mice but not in Group 2 mice. HIGH feeding in Group 3 did not compromise skeletal integrity. Taken together, propranolol attenuates HIGH-induced body weight increases while weight gain is in progress but not once obesity has already been established. HIGH feeding during the growth period results in compromised bone mass/architecture; which can be attenuated by propranolol administration during the growth period, but not by propranolol administration after obesity has already been established.