Epididymal Fat Pad Weight Research Articles

Dose‐Dependent Anti‐Inflammatory and Metabolic Effects of Eicosapentaenoic Acid in Diet‐Induced Obese Mice

Obesity is a widespread epidemic that increases the risk for several metabolic diseases such as diabetes and cardiovascular diseases. Long‐chain omega‐3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) possess anti‐inflammatory and potent triglyceride‐lowering properties at high doses (4–6 g/day). However, whether lower doses are effective in reducing metabolic alterations associated with obesity has not been investigated. The objective of this study is to determine dose‐dependent effects of EPA in diet‐induced obese mice. We used B6 male mice fed for 14 weeks a high‐fat diet (HF, 45% kcal fat) or HF diet supplemented with 36, 18, or 9 g/kg of AlaskOmega EPA‐enriched fish oil (800mg EPA/g fish oil), kindly provided by Organic Technologies. We conducted metabolic phenotyping during the feeding period, and harvested tissues and blood at termination. There were no differences in food intake across the four treatment groups. Only 36 g/kg of EPA significantly lowered body weight, fat content and epididymal fat pad weight (P<0.05), compared to HF. However, EPA at both 18 and 36 g/kg doses significantly increased glucose clearance and insulin sensitivity (P<0.05), compared to mice fed HF or 9 g/kg of EPA. Locomotor activity was significantly increased (P<0.05) in mice fed EPA 36 and 18 g/kg compared to other groups. Interestingly, compared to HF with all doses of EPA, energy expenditure and oxygen consumption were significantly increased (P<0.05); while serum insulin and leptin levels were significantly decreased (p<0.05). These results validate weight‐ and adiposity‐ independent metabolic benefits of EPA in obesity and demonstrate that doses of EPA comparable to those currently used to treat hypertriglyceridemia (18g/kg mouse diet, ~5g/d human diet) confer several metabolic benefits.Support or Funding InformationUSDA NIFA Postdoctoral Fellowship Grant # 2017‐07139

Gochujang prepared using rice and wheat koji partially alleviates high-fat diet-induced obesity in rats.

The aim of this study was to compare whether gochujang products prepared using giant embryo rice koji (rice gochujang, RG) and wheat koji (wheat gochujang, WG) have anti‐obesity effects on rats fed a high‐fat diet (HFD), who served as a model for obesity. The nutritional composition of RG and WG including proximate constituents, amino acid and fatty acid compositions were investigated. Consequently, the secondary fermented metabolites were analyzed in RG and WG by ultrahigh‐performance liquid chromatography and mass spectrometry. Rats were fed a HFD containing 10% RG powder (HFD‐RG) or 10% WG powder (HFD‐WG) for 8 weeks. Body weight gain, weights of liver, epididymal, retroperitoneal, perirenal, and total white fat pads, and levels of serum triglyceride (TG), total cholesterol, low‐density lipoprotein cholesterol, and leptin were lower in all gochujang groups than in the HFD group. Furthermore, RG and WG treatment decreased the hepatic TG content and lipid accumulation and significantly reduced the size of epididymal adipocytes. These effects are probably mediated through inhibition of hepatic fatty acid synthase, acetyl CoA carboxylase, malic enzyme, and adipose tissue lipoprotein lipase activities. The anti‐obesity effect was slightly greater in the HFD‐RG group than in the HFD‐WG group. This effect may be attributed to secondary metabolites, such as capsaicin, genistein, daidzein, soyasaponin, and lysophosphatidylcholines, contained in gochujang prepared using giant embryo rice or wheat koji.

Metformin improves vascular and metabolic insulin action in insulin-resistant muscle.

Insulin stimulates glucose disposal in skeletal muscle in part by increasing microvascular blood flow, and this effect is blunted during insulin resistance. We aimed to determine whether metformin treatment improves insulin-mediated glucose disposal and vascular insulin responsiveness in skeletal muscle of insulin-resistant rats. Sprague-Dawley rats were fed a normal (ND) or high-fat (HFD) diet for 4 weeks. A separate HFD group was given metformin in drinking water (HFD + MF, 150 mg/kg/day) during the final 2 weeks. After the intervention, overnight-fasted (food and metformin removed) anaesthetised rats underwent a 2-h euglycaemic-hyperinsulinaemic clamp (10 mU/min/kg) or saline infusion. Femoral artery blood flow, hindleg muscle microvascular blood flow, muscle glucose disposal and muscle signalling (Ser473-AKT and Thr172-AMPK phosphorylation) were measured. HFD rats had elevated body weight, epididymal fat pad weight, fasting plasma insulin and free fatty acid levels when compared to ND. HFD-fed animals displayed whole-body and skeletal muscle insulin resistance and blunting of insulin-stimulated femoral artery blood flow, muscle microvascular blood flow and skeletal muscle insulin-stimulated Ser473-AKT phosphorylation. Metformin treatment of HFD rats reduced fasting insulin and free fatty acid concentrations and lowered body weight and adiposity. During euglycaemic-hyperinsulinaemic clamp, metformin-treated animals showed improved vascular responsiveness to insulin, improved insulin-stimulated muscle Ser473-AKT phosphorylation but only partially restored (60%) muscle glucose uptake. This occurred without any detectable levels of metformin in plasma or change in muscle Thr172-AMPK phosphorylation. We conclude that 2-week metformin treatment is effective at improving vascular and metabolic insulin responsiveness in muscle of HFD-induced insulin-resistant rats.

Microbial and metabolomic remodeling by a formula of Sichuan dark tea improves hyperlipidemia in apoE-deficient mice.

Medicine-food homology is a long-standing concept in traditional Chinese medicine. YiNianKangBao (YNKB) tea is a medicine-food formulation based on Sichuan dark tea (Ya’an Tibetan tea), which is traditionally used for its lipid-lowering properties. In this study, we evaluated the effects of YNKB on dyslipidemia and investigated the mechanism underlying its correlation with gut microbiota and serum metabolite regulation. Wild-type mice were fed a normal diet as a control. Male ApoE-/- mice were randomly divided into three high-fat diet (HFD) groups, a model group, and two treated groups (100, 400 mg/kg/d for low, high-dose), and fed by gavage for 12 weeks. Serum lipid levels, composition of gut microbiota, and serum metabolites were then analyzed before treatment with YNKB. We extracted the ingredients of YNKB in boiled water for one hour. YNKB supplementation at a high dose of 400 mg/kg/day reduced bodyweight gains (relative epididymal fat pad and liver weight), and markedly attenuated serum lipid profiles and atherosclerosis index, with no significant differences present between the low-dose treatment and HFD groups. Gut microbiota and serum metabolic analysis indicated that significant differences were observed between normal, HFD, and YNKB treatment groups. These differences in gut microbiota exhibited strong correlations with dyslipidemia-related indexes and serum metabolite levels. Oral administration of high-dose YNKB also showed significant lipid-lowering activity against hyperlipidemia in apoE-deficient mice, which might be associated with composition alterations of the gut microbiota and changes in serum metabolite abundances. These findings highlight that YNKB as a medicine-food formulation derived from Sichuan dark tea could prevent dyslipidemia and improve the understanding of its mechanisms and the pharmacological rationale for preventive use.

Kidney osteoclast factors and matrix metalloproteinase expression in a mice model of diet-induced obesity and diabetes

The role of RANKL/RANK/OPG system on bone remodeling is well known, and there is evidence that it is also important to cardiovascular and kidney pathology, although the underlying mechanisms are not elucidated so far. Thus, we investigated in a mice model of diet-induced obesity and diabetes if renal histopathological changes are associated with the expression of RANKL/RANK/OPG system and matrix metalloproteinases (MMPs). Three months old C57BL/6 mice were fed with control (C) AIN93 M diet or high-fat high sucrose (HFHS) diets for 21 weeks (CEUA/UFF #647/15). The two groups presented weight gain, but it was higher in the HFHS group compared to the C group (+35%, P = 0.0001). The HFHS group also had increased epididymal, inguinal and retroperitoneal fat pad weight (+121%, P = 0.0006; +287%, P = 0.0007 and; +286%, P < 0.0001, respectively), and hyperglycemia (+43%, P = 0.02). The kidney of some HFHS fed mice displayed mononuclear inflammatory cell infiltrate (40%), perivascular fibrosis (20%), and focal tubule mineralization (20%). Glomeruli hypertrophy was not detected. Unexpectedly, OPG, RANK, MMP-2, and MMP-9 expression was not altered in HFHS groups (Western blot analysis). In conclusion, the expression of RANKL/RANK/OPG system proteins and MMPs was not influenced by diet-induced obesity and diabetes in the kidney of male C57BL/6 mice, although some adverse histopathological remodeling is noticed in the renal tissue.

Polylactose, a Novel Prebiotic Dietary Fiber, Reduces Adiposity and Hepatic Lipid Accumulation (P20-027-19)

ObjectivesPolylactose is a novel dietary fiber, synthesized by extrusion of lactose. To evaluate its potential as a prebiotic, we determined its fermentability, effect on the microbiome, and its effects on adiposity, fatty liver, and liver cholesterol in a diet-induced obesity animal model. Methods72 male Wistar rats were fed normal fat (NF) or high fat (HF, 51% fat by kcal) diets containing various fibers (6% fiber of interest and 3% cellulose, by weight); including cellulose (NFC and HFC), polylactose (HFPL), matched lactose (HFML), matched to the residual lactose in the HFPL diet, and two established prebiotic fibers, polydextrose (HFPD) and fructooligosaccharides (HFFOS). After 10 weeks on experimental diets, organs were harvested and cecal contents collected for analysis. ResultsThere were no significant differences in final body weights among the groups, nor did average daily food intake differ significantly among the HF-fed groups. HFPL animals had greater cecal weight (empty) and lower cecal contents pH when compared to all other groups, suggesting that polylactose is much more vigorously fermented than the other prebiotic fibers. This was also indicated by an increase in taxonomical abundance of probiotic species in the cecum. Epididymal fat pad weight was significantly decreased in the HFPL animals compared to all other HF groups (P < 0.05) and did not differ from the normal fat control (NFC). Liver lipids and cholesterol were significantly reduced in HFPL fed animals when compared to HFC fed animals and were numerically lower than all other HF groups. Transcriptome analysis of the liver revealed increased lipid oxidation and decrease lipid synthesis pathway expression, providing insights into mechanisms of reduction of lipid accumulation in the liver. ConclusionsPolylactose is a vigorously fermentable fiber and elicits a beneficial change in the gut microbiome. We also demonstrate that consuming polylactose, in the context of a high fat diet, prevents the accumulation of body fat normally seen with this diet, as well as reduced lipid and cholesterol accumulation in the liver. As these effects of polylactose were greater than those of two established prebiotics, fructooligosaccharides and polydextrose, this suggests that polylactose is a potent prebiotic. Funding SourcesMidwest Dairy Association.

Secondary Fermented Extract of Chaga-Cheonggukjang Attenuates the Effects of Obesity and Suppresses Inflammatory Response in the Liver and Spleen of High-Fat Diet-Induced Obese Mice.

Cheonggukjang and chaga mushrooms have numerous health benefits, and have been used in alternative medicine. Therefore, a powder mixture of 98: Cheonggukjang and 2: Chaga extracts was fermented with Lactobacillus acidophilus KCTC3925 (FCC) and its anti-obesity effects in high-fat diet (HFD)-induced obese mice were determined. Five-week-old male ICR mice were fed a normal diet or HFD in the presence or absence of 3% and 5% FCC by weight (n = 10 per group). After 12 weeks, the mice were sacrificed, and the serum and tissue samples were collected for analysis. Body weight and epididymal fat pad weight were significantly lowered in the 3% and 5% FCC groups compared with those in the HFD control group (p < 0.01). FCC supplementation suppressed serum triglyceride and increased serum HDL-C levels (p < 0.01). Serum GOT, GPT, and leptin levels, hepatic COX-2 mRNA expression, and splenic COX-2 and IL-4 mRNA expression were significantly higher in the HFD groups than in the control group (p > 0.05); however, except for splenic IL-4 levels, the increases were significantly attenuated by FCC supplementation. Expression of ICAM-1, an aortic inflammatory marker, was significantly increased in the HFD group; this effect was suppressed in the 3% FCC group (p < 0.01) but not in the 5% FCC group. FCC suppressed the body weight and epididymal fat pad weight gain, as well as inflammatory responses in the liver and spleen of HFD-fed mice. Thus, FCC supplementation will be beneficial for the treatment of obesity-related effects.

Scutellaria baicalensis Alleviates Insulin Resistance in Diet-Induced Obese Mice by Modulating Inflammation.

Insulin resistance is strongly associated with the metabolic syndrome, and chronic inflammation is known to be a major mechanism of insulin resistance and is a therapeutic target. This study was designed to evaluate the effect of Scutellaria baicalensis (SB) in high-fat diet (HFD)-induced insulin-resistant mice and to investigate its mechanism based on inflammatory responses. Mice were fed a HFD to induce insulin resistance and then administered SB for nine weeks. Body weight, glucose, lipid, insulin, epididymal fat pad and liver weights, and histologic characteristics were evaluated to determine the effect on insulin resistance. In order to evaluate the effects on the inflammatory process, we analyzed the proportions of macrophages in liver and epididymal fat and measured inflammatory gene expression. Fasting and postprandial glucose, fasting insulin, HOMA-IR, triglycerides, and low density lipoprotein cholesterol levels were significantly decreased by SB administration. The epididymal fat and liver showed significant weight decreases and histological improvements. Total adipose tissue macrophages (ATMs) decreased (27.71 ± 3.47% vs. 45.26 ± 7.26%, p < 0.05), M2 ATMs increased (47.02 ± 6.63% vs. 24.28 ± 8.00%, p < 0.05), and CD11b+ Kupffer cells decreased. The expression levels of tumor necrosis factor alpha and F4/80 in the liver were significantly decreased (12.03 ± 1.47% vs. 25.88 ± 4.57%, p < 0.05) compared to HFD group. These results suggest that SB improved insulin resistance through inhibition of macrophage-mediated inflammation.

Telmisartan is effective to ameliorate metabolic syndrome in rat model - a preclinical report.

BackgroundMetabolic syndrome (MS) is known to be associated with hypertension, insulin resistance, and dyslipidemia, and it raises the risk for cardiovascular diseases and diabetes mellitus. Telmisartan is used in clinic as an angiotensin II receptor blocker and it is also identified as activating peroxisome proliferator-activated receptors δ (PPARδ). Activation of PPARδ produced beneficial effects on fatty acid metabolism and glucose metabolism. This study aims to investigate the effects of telmisartan on the modulation of MS in rats fed a high-fat/high-sodium diet.MethodsRats were fed with a high-fat/high-sodium diet and received injections of streptozotocin at low dose to induce MS. Then, rats with MS were treated with telmisartan. The weight, glucose tolerance, and insulin sensitivity were measured. The lipid profiles were also obtained. The weights of retroperitoneal and epididymal fat pads were determined. The role of PPARδ in telmisartan treatment was identified in rats pretreated with the specific antagonist GSK0660.ResultsThe results showed that telmisartan, but not losartan, significantly reduced plasma glucose and plasma insulin, and improved insulin resistance in rats with MS. Telmisartan also decreased blood pressure and lipids more significantly than losartan. Moreover, GSK0660 effectively reversed the effects of telmisartan in the MS rats. In the MS group, telmisartan activated PPARδ to enhance the levels of phosphorylated GLUT4 in muscle or the expression of phosphoenolpyruvate carboxykinase (PEPCK) in the liver, which was also abolished by GSK0660. Telmisartan is useful to ameliorate hypertension and insulin resistance in rats with MS. Telmisartan improves the insulin resistance through increased expression of GLUT4 and down-regulation of PEPCK via PPARδ-dependent mechanisms.ConclusionTelmisartan has been proven to ameliorate MS, particularly in the prediabetes state. Therefore, telmisartan is suitable to develop for the management of MS in clinics.

Tart Cherry Reduces Inflammation in Adipose Tissue of Zucker Fatty Rats and Cultured 3T3-L1 Adipocytes.

Obesity increases adipose tissue inflammation and secretion of pro-inflammatory adipokines, which have systemic effects on the organism’s health status. Our objective was to dissect mechanisms of anti-inflammatory effects of tart cherry (TC) in adipose tissue of Zucker fatty rats, and cultured 3T3-L1 adipocytes. Rats were fed either a control diet, or 4% TC powder diets for eight weeks. Body and epididymal fat pad weights were not significantly different between control and TC groups. However, rats fed the TC diet had significantly reduced adipose tissue inflammation (p < 0.05), as determined by reduced mRNA levels of pro-inflammatory markers including interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), interleukin-1beta (IL-1β), monocyte chemoattractant protein 1 (MCP-1), inducible nitric oxide synthase (iNOS), and CD-11b, and increased mRNA levels of type-1 arginase (Arg-1) anti-inflammatory marker. Consistent with these in vivo results, TC significantly decreased expression of IL-6 mRNA and protein levels in lipopolysaccharide (LPS) stimulated adipocytes compared to those stimulated with LPS, but no TC. Moreover, both in vivo (rat adipose tissue) and in vitro (3T3-L1 adipocytes), phosphorylation of p65-NF-κB subunit was significantly reduced by TC. Additionally, TC decreased mRNA expression of fatty acid synthase (FASN), and increased expression of peroxisome proliferator-activated receptor alpha (PPARα), master regulator of lipid oxidation, and anti-oxidant markers nuclear factor erythroid-derived 2-related factor (NRFs) in both models. In conclusion, our findings indicate that TC downregulates inflammation in part via the nuclear factor kappa B (NF-κB) pathway in adipose tissue. Thus, TC may serve as a potential intervention to reduce obesity-associated inflammation.

Chronic Electrical Stimulation at Acupoints Reduces Body Weight and Improves Blood Glucose in Obese Rats via Autonomic Pathway

The aim of this study was to investigate effects and mechanisms of chronic electrical stimulation at acupoints (CEA) using surgically implanted electrodes on food intake, body weight, and metabolisms in diet-induced obese (DIO) rats. Thirty-six DIO rats were chronically implanted with electrodes at acupoints ST-36 (Zusanli). Three sets of parameters were tested: electrical acupuncture (EA) 1 (2-s on, 3-s off, 0.5 ms, 15 Hz, 6 mA), EA2 (same as EA1 but continuous pulses), and EA3 (same as EA2 but 10 mA). A chronic study was then performed to investigate the effects of CEA on body weight and mechanisms involving gastrointestinal hormones and autonomic functions. EA2 significantly reduced food intake without uncomfortable behaviors. CEA at EA2 reduced body weight and epididymal fat pad weight (P < 0.05). CEA reduced both postprandial blood glucose and HbA1c (P < 0.05). CEA delayed gastric emptying (P < 0.03) and increased small intestinal transit (P < 0.02). CEA increased fasting plasma level of glucagon-like peptide-1 (GLP-1) and peptide YY (P < 0.05); the increase of GLP-1 was inversely correlated with postprandial blood glucose (R 2 = 0.89, P < 0.05); and the plasma ghrelin level remained unchanged. EA increased sympathetic activity (P < 0.01) and reduced vagal activity (P < 0.01). CEA at ST-36 reduces body weight and improves blood glucose possibly attributed to multiple mechanisms involving gastrointestinal motility and hormones via the autonomic pathway.

The Effect of Magnolia Bark on the Metabolic Inflammation and Insulin Resistance of ob/ob Mice

Objective This study was undertaken to investigate how magnolia bark extract affects ob/ob mouse in terms of metabolic inflammation and insulin resistance. Methods Leptin-deficient ob/ob mice were divided into 2 groups (n=5): a normal saline treatment (=control) and magnolia bark treatment. Wild type mice were the lean group (n=5). After 5 weeks, we measured fasting blood sugar (FBS) and conducted oral glucose tolerance tests (OGTTs) in each group. After 6 weeks, we measured body weight, epididymal fat pad weight, liver weight, serum glucose, serum insulin, and gene expression of tumor necrosis factor-α, interferon-γ, and interleukin-6. We characterized the phenotype of adipose tissue macrophages (ATMs) and analyzed fractions of the phenotype in each group by flow cytometry. Results In the magnolia bark group, fasting blood sugar, oral glucose tolerance levels, and insulin resistance (HOMA-IR) were significantly decreased. The population and proportion of ATMs among leukocytes in adipose tissue were significantly decreased in the magnolia bark group. The population and proportion of M1 type ATMs among ATMs were significantly decreased in the magnolia bark group. Gene expression of tumor necrosis factor-α was significantly decreased in the magnolia bark group. Conclusions These results support a positive effect of magnolia bark on metabolic diseases such as insulin resistance and metabolic inflammation in leptin-deficient ob/ob mice. Keywords: magnolia bark, ob/ob mouse, metabolic inflammation, insulin resistance, ATMs

Nordihydroguaiaretic Acid, a Lignan from Larrea tridentata (Creosote Bush), Protects Against American Lifestyle-Induced Obesity Syndrome Diet-Induced Metabolic Dysfunction in Mice.

To determine the effects of nordihydroguaiaretic acid (NDGA) on metabolic and molecular changes in response to feeding a typical American fast food or Western diet, mice were fed an American lifestyle-induced obesity syndrome (ALIOS) diet and subjected to metabolic analysis. Male C57BL/6J mice were randomly assigned to the ALIOS diet, the ALIOS diet supplemented with NDGA (NDGA+ALIOS), or a control diet and were maintained on the specific diet for 8 weeks. Mice fed the ALIOS diet showed increased body, liver, and epididymal fat pad weight as well as increased plasma alanine transaminase (ALT) and aspartate aminotransferase (AST) levels (a measure of liver injury) and liver triglyceride content. Coadministration of NDGA normalized body and epididymal fat pad weight, ALT and AST levels, and liver triglycerides. NDGA treatment also improved insulin sensitivity but not glucose intolerance in mice fed the ALIOS diet. In mice fed the NDGA+ALIOS diet, NDGA supplementation induced peroxisome proliferator-activated receptor α (PPARα; the master regulator of fatty acid oxidation) and mRNA levels of carnitine palmitoyltransferases Cpt1c and Cpt2, key genes involved in fatty acid oxidation, compared with the ALIOS diet. NDGA significantly reduced liver endoplasmic reticulum (ER) stress response C/EBP homologous protein, compared with chow or the ALIOS diet, and also ameliorated ALIOS diet-induced elevation of apoptosis signaling protein, caspase 3. Likewise, NDGA downregulated the ALIOS diet-induced mRNA levels of Pparg, fatty acid synthase Fasn, and diacylglycerol acyltransferase Dgat2 NDGA treatment of ALIOS-fed mice upregulated the hepatic expression of antioxidant enzymes, glutathione peroxidase 4, and peroxiredoxin 3 proteins. In conclusion, we provide evidence that NDGA improves metabolic dysregulation by simultaneously modulating the PPARα transcription factor and key genes involved in fatty acid oxidation, key antioxidant and lipogenic enzymes, and apoptosis and ER stress signaling pathways.

Anti-obesity effects of Clausena excavata in high-fat diet-induced obese mice

Clausena excavata (C. excavata) has been used as a traditional medicine for the treatment of abdominal pain, enteritis, dysentery, and malaria. The present study was designed to evaluate the effect of a 50% ethanol extract of C. excavata (ECE) on weight loss, adipocyte size, and obesity-related biochemical parameters in high-fat diet (HFD)-induced obese mice. After 6 weeks of HFD + ECE administration, HFD-induced total fat, subcutaneous fat, and visceral fat were evaluated by micro-computed tomography. The serum levels of triglyceride (TG), total cholesterol (TCH), high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol were evaluated with a biochemical analyzer, and leptin and adiponectin levels in the serum were assessed via enzyme-linked immunoassay (ELISA). Moreover, adipocyte size and lipid formation in the liver were examined. We found that weight gain, epididymal fat pad weight, adipocyte size, and lipid formation were markedly attenuated in the livers of HFD-induced obese mice treated with ECE. Furthermore, TG, TCH, and leptin decreased in the serum, whereas adiponectin increased. In conclusion, our data show that ECE has potent anti-obesity activity in vivo and support the development of ECE as a potential therapeutic agent for the treatment of obesity.

Targeted Deletion of Adipocyte Abca1 (ATP-Binding Cassette Transporter A1) Impairs Diet-Induced Obesity.

Adipose tissue cholesterol increases with adipocyte triglyceride content and size during development of obesity. However, how adipocyte cholesterol affects adipocyte function is poorly understood. The aim of this study was to evaluate the role of the cellular cholesterol exporter, Abca1 (ATP-binding cassette transporter A1), on adipose tissue function during diet-induced obesity. Adiponectin Cre recombinase transgenic mice were crossed with Abca1flox/flox mice to generate ASKO (adipocyte-specific Abca1 knockout) mice. Control and ASKO mice were then fed a high-fat, high-cholesterol (45% calories as fat and 0.2% cholesterol) diet for 16 weeks. Compared with control mice, ASKO mice had a 2-fold increase in adipocyte plasma membrane cholesterol content and significantly lower body weight, epididymal fat pad weight, and adipocyte size. ASKO versus control adipose tissue had decreased PPARγ (peroxisome proliferator-activated receptor γ) and CCAAT/enhancer-binding protein expression, nuclear SREBP1 (sterol regulatory element-binding protein 1) protein, lipogenesis, and triglyceride accretion but similar Akt activation after acute insulin stimulation. Acute siRNA-mediated Abca1 silencing during 3T3L1 adipocyte differentiation reduced adipocyte Abca1 and PPARγ protein expression and triglyceride content. Systemic stimulated triglyceride lipolysis and glucose homeostasis were similar between control and ASKO mice. Adipocyte Abca1 is a key regulator of adipocyte lipogenesis and lipid accretion, likely because of increased adipose tissue membrane cholesterol, resulting in decreased activation of lipogenic transcription factors PPARγ and SREBP1.

Immune profiles of T lymphocyte subsets in adipose tissue of obese mouse induced by high-fat diet

In this study, we analyzed high-fat diet (HFD)-induced time-course changes in proportions of T lymphocyte subsets in adipose tissue.Mice were fed with normal-fat diet (NFD) or HFD for 20 weeks. An autoanalyzer was used to assay plasma concentrations of glucose, cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Stromal vascular cells were isolated from epididymal adipose tissues and labeled with antibodies for cluster of differentiation (CD) 3, CD4, CD8, interferon -g, interleukin (IL)-4, and IL-17 for fluorescence-activated cell sorter. We discovered that weight of epididymal fat pads and perirenal fat in HFD group were higher than that in NFD group. Significant changes in glucose, cholesterol, triglyceride, LDL, and HDL content were detected in sera of mice fed with HFD compared with those provided with NFD. Proportions of CD3+, CD4+, and CD8+ T cells increased significantly in adipose tissues of HFD mice compared with those of NFD mice. Proportions of T helper (Th)1 and Th17 sublineages also increased significantly in HFD group. Long-time HFD-induced obesity can increase proportions of CD3+ T, CD4+ T, and CD8+ T cells in epididymal fat pads, disrupt balance of CD4+ T lymphocyte subsets, and induce progressive Th1 and Th17 biases.

Immune profiles of T lymphocyte subsets in adipose tissue of obese mouse induced by high-fat diet

In this study, we analyzed high-fat diet (HFD)-induced time-course changes in proportions of T lymphocyte subsets in adipose tissue.Mice were fed with normal-fat diet (NFD) or HFD for 20 weeks. An autoanalyzer was used to assay plasma concentrations of glucose, cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Stromal vascular cells were isolated from epididymal adipose tissues and labeled with antibodies for cluster of differentiation (CD) 3, CD4, CD8, interferon -g, interleukin (IL)-4, and IL-17 for fluorescence-activated cell sorter. We discovered that weight of epididymal fat pads and perirenal fat in HFD group were higher than that in NFD group. Significant changes in glucose, cholesterol, triglyceride, LDL, and HDL content were detected in sera of mice fed with HFD compared with those provided with NFD. Proportions of CD3+, CD4+, and CD8+ T cells increased significantly in adipose tissues of HFD mice compared with those of NFD mice. Proportions of T helper (Th)1 and Th17 sublineages also increased significantly in HFD group. Long-time HFD-induced obesity can increase proportions of CD3+ T, CD4+ T, and CD8+ T cells in epididymal fat pads, disrupt balance of CD4+ T lymphocyte subsets, and induce progressive Th1 and Th17 biases.

An Optimized IES Method and Its Inhibitory Effects and Mechanisms on Food Intake and Body Weight in Diet-Induced Obese Rats: IES for Obesity.

This paper aims to optimize stimulation parameters and durations for intestinal electrical stimulation (IES) and to explore the effects and mechanisms of chronic IES with optimized methodology in obesity rats. Sixteen diet-induced obese (DIO) rats were tested for food intake with four different sets of IES parameters each lasting 1week. Then, another 12 DIO rats were used to test the effect of IES on food intake with different stimulation durations. Finally, 16 DIO rats were treated with IES or sham-IES for 4weeks. Meal patterns, food intake, and body weight were observed. Mechanisms involving gastrointestinal motility, ghrelin, and glucagon-like peptide-1 (GLP-1) were studied. (1) Acute IES with different parameters showed different inhibitory effects on food intake, and the most effective parameters were 0.6s on, 0.9s off, 80Hz, 2ms, and 4mA with which 26.3% decrease in food intake was noted (p<0.001). (2) IES with daily treatment of 12h was most effective in suppressing food intake compared with 1 or 6h. (3) Four-week IES reduced net weight by 10.9% (p<0.05 vs. sham-IES) and epididymal fat pad weight by 13.9% (p<0.001). (4) IES delayed gastric emptying (p<0.001) and accelerated intestinal transit (p<0.05). (5) IES increased both fasting and postprandial plasma levels of GLP-1 but not ghrelin. Twelve-hour daily IES using optimized stimulation parameters reduces food intake and body weight in DIO rats by altering gastrointestinal motility and GLP-1. The IES methodology derived in this study may have a therapeutic potential for obesity.

Kefir prevented excess fat accumulation in diet-induced obese mice.

Excessive body fat accumulation can result in obesity, which is a serious health concern. Kefir, a probiotic, has recently shown possible health benefits in fighting obesity. This study investigated the inhibitory effects of 0.1 and 0.2% kefir powder on fat accumulation in adipose and liver tissues of high-fat diet (HFD)-induced obese mice. Kefir reduced body weight and epididymal fat pad weight and decreased adipocyte diameters in HFD-induced obese mice. This was supported by decreased expression of genes related to adipogenesis and lipogenesis as well as reduced proinflammatory marker levels in epididymal fat. Along with reduced hepatic triacylglycerol concentrations and serum alanine transaminase and aspartate transaminase activities, genes related to lipogenesis and fatty acid oxidation were downregulated and upregulated, respectively, in liver tissue. Kefir also decreased serum triacylglycerol, total cholesterol, and low-density lipoprotein-cholesterol concentrations. Overall, kefir has the potential to prevent obesity.

Potential involvement of dietary advanced glycation end products in impairment of skeletal muscle growth and muscle contractile function in mice.

Diets enriched with advanced glycation end products (AGE) have recently been related to muscle dysfunction processes. However, it remains unclear whether long-term exposure to an AGE-enriched diet impacts physiological characteristics of skeletal muscles. Therefore, we explored the differences in skeletal muscle mass, contractile function and molecular responses between mice receiving a diet high in AGE (H-AGE) and low in AGE (L-AGE) for 16 weeks. There were no significant differences between L-AGE and H-AGE mice with regard to body weight, food intake or epididymal fat pad weight. However, extensor digitorum longus (EDL) and plantaris (PLA) muscle weights in H-AGE mice were lower compared with L-AGE mice. Higher levels of N ε -(carboxymethyl)-l-lysine, a marker for AGE, in EDL muscles of H-AGE mice were observed compared with L-AGE mice. H-AGE mice showed lower muscle strength and endurance in vivo and lower muscle force production of PLA muscle in vitro. mRNA expression levels of myogenic factors including myogenic factor 5 and myogenic differentiation in EDL muscle were lower in H-AGE mice compared with L-AGE mice. The phosphorylation status of 70-kDa ribosomal protein S6 kinase Thr389, an indicator of protein synthesis signalling, was lower in EDL muscle of H-AGE mice than that of L-AGE mice. These findings suggest that long-term exposure to an AGE-enriched diet impairs skeletal muscle growth and muscle contractile function, and that these muscle dysfunctions may be attributed to the inhibition of myogenic potential and protein synthesis.