Epididymal Fat Pad Weight Research Articles

Low-gainer diet-induced obese microbiota transplanted mice exhibit increased fighting.

Weight gain variation is a great challenge in diet-induced obesity studies since low-gainer animals are of limited experimental value. The inbred C57BL/6 (B6) mice are frequently used models due to their genetic homogeneity and susceptibility to diet-induced obesity (DIO). The aim of this study is to investigate if the gut microbiota (GM) influences the fraction of low weight gainers in DIO studies. A total of 100 male B6 mice (donor population) were fed a high-fat diet for 14 weeks and divided into the study groups high gainer (HG) and low gainer (LG) based on their weight gain. Subsequently, fecal matter transplantation (FMT) was done on germ-free B6 mice with GM from HG and LG donors (FMT population). LG (13.35 ± 2.5 g) and HG (25.52 ± 2.0 g) animals were identified by the weight gain from week 1 to week 12. Interestingly, the start weight of the LG (20.36 ± 1.4 g) and HG (21.59 ± 0.7 g) groups differed significantly. Transplanting LG or HG fecal matter to germ-free mice resulted in significant differences in weight gain between HG and LG, as well as differences in serum leptin levels and epididymal fat pad weight. A clear LG-specific GM composition could not be distinguished by 16S rRNA gene amplicon sequencing. Surprisingly, significantly more fighting was recorded in LG groups of both donor populations and when transplanted to germ-free mice. The HG and LG phenotypes could be transferred to germ-free mice. The increased fighting in the LG group in both studies suggests not only that the tendency to fight can be transferred by FMT in these mice, but also that fighting should be prevented in DIO studies to minimize the number of LG animals.

MIR204 POTENTIALLY PROMOTES NON-ALCOHOLIC FATTY LIVER DISEASE BY INHIBITION OF CPT1A IN MOUSE HEPATOCYTES

Objective: Non-alcoholic fatty liver disease (NAFLD) is associated with hepatic metabolism dysfunction. However, the mechanistic role of miR204 in the development of NAFLD is unknown. We investigated the functional significance of miR204 in the evolution of NAFLD. Design and method: NAFLD was induced in isocitrate dehydrogenase (IDH2) knockout (KO) mice by feeding them with a high-fat diet (HFD). Blood parameters and hepatic fat accumulation were evaluated in IDH2 KO mice and wild-type (WT) mice. A miR204 inhibitor was subcutaneously injected into mice using an osmotic pump. The expression of miR204 was analyzed by quantitative PCR (qPCR). Results: IDH2 KO mice fed a normal diet (ND) or HFD showed significantly increased body weight, epididymal fat-pad weight, cholesterol, triglyceride, and macrophage marker (CD68), and inflammatory cytokine [tumor necrosis factor-a (TNF-a), interleukin (IL)-6 and IL-1b] expression compared to WT mice fed a ND or HFD. Moreover, the expression of miR204 was significantly increased in mice with IDH2 deficiency. miR204 regulates carnitine palmitoyltransferase 1a (cpt1a) synthesis, which inhibits fatty acid b-oxidation. Inhibition of miR204 prevents the disassembly of two fatty acid-related genes—peroxisomal acyl-coenzyme A oxidase 1 (ACOX-1) and peroxisome proliferator-activated receptor alpha (PPARa)—by activating CPT1a expression, which decreases inflammatory cytokines, epididymal fat pad weight, cholesterol, low-density lipoprotein (LDL), and triglycerides. Conclusions: miR204 promotes the pathogenesis of HFD-induced NAFLD by regulating hepatic metabolism and inflammation.

Early Treatment of Obese (ob/ob) Mice with Triiodothyronine Increases Oxidative Metabolism in Muscle but not in Brown Adipose Tissue or Liver

We explored the possibility that early replacement of low triiodothyronine (T3) may improve the low oxidative metabolism in metabolically important tissues of ob/ob mice. Triiodothyronine doses (2.5 to 25.0 μg/100 g body wt) were injected intraperitoneally into ob/ob and non-ob/ob mice daily from 3 wk until 6 wk of age. Untreated ob/ob and non-ob/ob mice were injected with saline (pH 9.1). Food intake was equalized across all groups. At 6 wk of age, the O2 consumption of muscle, white and brown adipose tissues, and hepatocytes was measured. The saline-treated ob/ob mice showed lower muscle weights, higher fat pad and liver weights, and larger fat cell sizes than saline-treated non-ob/ob mice. In ob/ob mice, tissue O2 consumption was the same in muscle, lower in brown and white adipose tissues, but higher in liver compared with values in non-ob/ob mice. Triiodothyronine treatment in ob/ob mice resulted in lower values for body weight, liver weight, hepatocyte number, liver protein, epididymal fat pad weight, and white adipocyte number and size than in saline-treated ob/ob mice. Triiodothyronine treatment increased soleus muscle, liver and brown adipose tissue O2 consumption in non-ob/ob mice. In ob/ob mice, triiodothyronine increased only soleus muscle O2 consumption and required higher doses than in non-ob/ob mice to achieve an effect. These data are consistent with the concept of tissue triiodothyronine resistance in ob/ob mice. Low triiodothyronine levels and tissue resistance to triiodothyronine might be important early defects in this obesity syndrome.

Resistant Starch Decreases Serum Total Cholesterol and Triacylglycerol Concentrations in Rats

Rats were meal-fed semipurified diets containing a low (0.8 g/MJ) and a high (9.6 g/MJ) amount of resistant starch (RS) or various amounts of RS (0.8 to 9.6 g/MJ) and guar gum (0 to 8.8 g/MJ). In one experiment, rats were fed the low and high RS diets in three dietary regimens (ad libitum consuming, 12 h ad libitum/12 h food deprived, and meal fed). Effects of RS and guar gum on serum postprandial and postabsorptive concentrations of total cholesterol (TC) and triacylglycerol (TAG), growth, hydrogen excretion, tissue weights and contents of small intestine and cecum, and pH of cecal contents were investigated. In addition, effects of RS on food intake, de novo hepatic synthesis of fatty acids and neutral sterols, and on lipoprotein lipase activity and weight of epididymal fat pads were investigated. Compared with feeding the low RS diet, the high RS diet reduced the serum TC and TAG concentrations, with these effects observed after 1 and 2 wk of feeding, respectively. The dietary regimen did not influence the effect of RS on the serum TC and TAG concentrations, but it did affect the serum TAG concentration. Resistant starch had no effect on the hepatic synthesis of fatty acids and neutral sterols or on the lipoprotein lipase activity in epididymal fat pads. Guar gum also reduced the serum TC concentration, but it had no effect on serum TAG concentration. The tissue weights and contents of small intestine and cecum as well as hydrogen excretion increased with increasing amounts of dietary RS and guar gum, whereas the pH of cecal contents decreased. No effects of RS on food intake and total body weight gain were found, whereas guar gum decreased weight gain. Feeding the high RS diet also led to a lower weight of the epididymal fat pads. We conclude that dietary RS can reduce serum TC and TAG concentrations and fat accretion.

Selection for Body Composition Does Not Affect Energetic Efficiency of Jejunal Glucose Uptake in Mice

Five-wk-old male mice from three lines were used to examine whether the apparent energetic efficiency of active jejunal glucose uptake in mouse jejunum is altered by genetic selection for different body composition. The mice lines were selected as follows: HE, high percentage of body fat with no change in body weight as a constraint; LF, low percentage of body fat; and RS, randomly bred control. Body weight was similar in all lines. Total jejunal O2 consumption and ouabain-sensitive O2 consumption were used to estimate the energy expenditure associated with glucose absorption and Na+/K+-ATPase activity. Tritiated 3-O-methyl-D-glucose was used to determine glucose uptake by mouse jejunum. Line LF, when compared with line HE, had lower body fat as indicated by epididymal fat pad weight (143 vs. 362 mg/mouse, P < 0.001). There were no significant differences in small intestinal weight, length and density (mg/cm) between LF and HE lines. Jejunal villus width was greater in line LF compared with line HE (115 vs. 92 µm, P < 0.002). Jejunal glucose transport and O2 consumption were not different between LF and HE lines. Ouabain-sensitive O2 consumption was not significantly different among the three lines. No differences were noted in the apparent energetic efficiency of active glucose uptake among lines.

MiR204 potentially promotes non-alcoholic fatty liver disease by inhibition of cpt1a in mouse hepatocytes

Non-alcoholic fatty liver disease (NAFLD) is associated with hepatic metabolism dysfunction. However, the mechanistic role of miR204 in the development of NAFLD is unknown. We investigate the functional significance of miR204 in the evolution of NAFLD. IDH2 KO mice feed a normal diet (ND) or HFD increased body weight, epididymal fat-pad weight, lipid droplet in liver, blood parameter and inflammation compared to WT mice fed a ND or HFD. Moreover, the expression of miR204 is increased in mice with IDH2 deficiency. Increased miR204 by IDH2 deficiency regulates carnitine palmitoyltransferase 1a (cpt1a) synthesis, which inhibits fatty acid β-oxidation. Inhibition of miR204 prevents the disassembly of two fatty acid-related genes by activating CPT1a expression, which decreases lipid droplet in liver, inflammatory cytokines, epididymal fat pad weight, blood parameters. Increased miR204 by IDH2 deficiency promotes the pathogenesis of HFD-induced NAFLD by regulating hepatic fatty acid metabolism and inflammation.

Latent transforming growth factor β binding protein 3 controls adipogenesis

Transforming growth factor-beta (TGFβ) is released from cells as part of a trimeric latent complex consisting of TGFβ, the TGFβ propeptides, and either a latent TGFβ binding protein (LTBP) or glycoprotein-A repetitions predominant (GARP) protein. LTBP1 and 3 modulate latent TGFβ function with respect to secretion, matrix localization, and activation and, therefore, are vital for the proper function of the cytokine in a number of tissues. TGFβ modulates stem cell differentiation into adipocytes (adipogenesis), but the potential role of LTBPs in this process has not been studied. We observed that 72 h post adipogenesis initiation Ltbp1, 2, and 4 expression levels decrease by 74–84%, whereas Ltbp3 expression levels remain constant during adipogenesis. We found that LTBP3 silencing in C3H/10T1/2 cells reduced adipogenesis, as measured by the percentage of cells with lipid vesicles and the expression of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ). Lentiviral mediated expression of an Ltbp3 mRNA resistant to siRNA targeting rescued the phenotype, validating siRNA specificity. Knockdown (KD) of Ltbp3 expression in 3T3-L1, M2, and primary bone marrow stromal cells (BMSC) indicated a similar requirement for Ltbp3. Epididymal and inguinal white adipose tissue fat pad weights of Ltbp3−/- mice were reduced by 62% and 57%, respectively, compared to wild-type mice. Inhibition of adipogenic differentiation upon LTBP3 loss is mediated by TGFβ, as TGFβ neutralizing antibody and TGFβ receptor I kinase blockade rescue the LTBP3 KD phenotype. These results indicate that LTBP3 has a TGFβ-dependent function in adipogenesis both in vitro and possibly in vivo. SignificanceUnderstanding the control of mesenchymal stem cell fate is crucial for the potential use of these cells for regenerative medicine.

Wild Rice and Brown Rice Reduce Liver and Serum Lipids in Wistar Rats fed Either a Total Western Diet or a High Fat Diet

ObjectivesNon-alcoholic fatty liver disease (NAFLD) prevalence is increasing, and no pharmacological intervention exists to treat it. Here, we determined the effect of feeding wild rice and brown rice on liver lipids and the gut microbiome when fed two different high fat background diets meant to induce fatty liver. MethodsIn the HFD trial, male Wistar rats (n = 8 per group) were fed either a high fat diet (HF), or a HF containing either 20% wild rice (WR) or 20% brown rice (BR) for 8 weeks. Cecal contents, liver, and epididymal fat pads were harvested. Microbiome analysis of cecal contents was conducted by 16S sequencing. In the TWD trial, male Wistar rats (n = 12 per group) were fed the AIN-93G diet (Basal), the Total Western Diet (TWD; a high fat diet that mimics the average American diet), or the TWD containing 30% WR (WR) for 10 weeks, then liver and epididymal fat pads were harvested. ResultsIn the HFD trial, both WR and BR significantly reduced total liver lipids compared to HF (p < 0.0001). However, epididymal fat pad weight was not reduced in either of the rice groups compared to HF (p > 0.05). Serum cholesterol was also reduced in WR compared to HF (p < 0.0188). In the TWD trial, the TWD elevated total liver lipids compared to Basal, but WR reduced liver lipids significantly (p < o.oo6) compared to TWD. WR did not lower epididymal fat pad weight (p > 0.1) compared to TWD. Additionally, p-AMPK/AMPK was increased in WR compared to TWD (p < 0.003). This shift in AMPK activation was not seen in the HFD trial (p > 0.05). In the HFD trial microbiome analysis, the beta-diversity measure of community dissimilarity indicated that WR had a significantly different microbial profile compared to the animals fed the HF diet (p < 0.003) while BR had an increased abundance of lactobacillus (p < 0.03) compared to animals fed the HF diet. ConclusionsWild rice feeding reduced fatty liver, using two different high fat background diets, and altered the gut microbiome. Wild rice should be further explored as a dietary approach to prevent development of non-alcoholic fatty liver disease (NAFLD), and to investigate whether hepatic lipid reductions are mediated by changes in the gut microbiome. Funding SourcesThe TWD trial was sponsored by the Whiteside Institute for Clinical Research and the HFD trial was sponsored by the Minnesota Cultivated Wild Rice Council.

Diabetogenic and Obesogenic Effects of Cadmium in Db/Db Mice and Rats at a Clinically Relevant Level of Exposure.

Studies show an association between cadmium (Cd) exposure and prediabetes or type II diabetes mellitus. We have previously reported that Cd causes decreased levels of serum leptin in rats following 12 weeks of daily Cd dosing (0.6 mg/kg/b.w./day). Since leptin plays an important role in metabolism, we examined the effects of Cd on rats and db/db mice, which are deficient in leptin receptor activity. We gave rats and mice daily subcutaneous injections of saline (control) or CdCl2 at a dose of 0.6 mg/kg of Cd for 2 weeks, followed by 2 weeks of no dosing. At the end of the 4-week study, exposure to Cd resulted in a more rapid increase in blood glucose levels following an oral glucose tolerance test in db/db vs. lean mice. During the two weeks of no Cd dosing, individual rat bodyweight gain was greater (p ≤ 0.05) in Cd-treated animals. At this time point, the combined epididymal and retroperitoneal fat pad weight was significantly greater (p ≤ 0.05) in the Cd-treated lean mice compared to saline-treated controls. Although this pilot study had relatively low N values (4 per treatment group for mice and 6 for rats) the results show that clinically relevant levels of Cd exposure resulted in diabetogenic as well as obesogenic effects.

Hepatic Transcriptome Profiling Reveals Lack of Acsm3 Expression in Polydactylous Rats with High-Fat Diet-Induced Hypertriglyceridemia and Visceral Fat Accumulation.

Metabolic syndrome (MetS) is an important cause of worldwide morbidity and mortality. Its complex pathogenesis includes, on the one hand, sedentary lifestyle and high caloric intake, and, on the other hand, there is a clear genetic predisposition. PD (Polydactylous rat) is an animal model of hypertriglyceridemia, insulin resistance, and obesity. To unravel the genetic and pathophysiologic background of this phenotype, we compared morphometric and metabolic parameters as well as liver transcriptomes among PD, spontaneously hypertensive rat, and Brown Norway (BN) strains fed a high-fat diet (HFD). After 4 weeks of HFD, PD rats displayed marked hypertriglyceridemia but without the expected hepatic steatosis. Moreover, the PD strain showed significant weight gain, including increased weight of retroperitoneal and epididymal fat pads, and impaired glucose tolerance. In the liver transcriptome, we found 5480 differentially expressed genes, which were enriched for pathways involved in fatty acid beta and omega oxidation, glucocorticoid metabolism, oxidative stress, complement activation, triacylglycerol and lipid droplets synthesis, focal adhesion, prostaglandin synthesis, interferon signaling, and tricarboxylic acid cycle pathways. Interestingly, the PD strain, contrary to SHR and BN rats, did not express the Acsm3 (acyl-CoA synthetase medium-chain family member 3) gene in the liver. Together, these results suggest disturbances in fatty acid utilization as a molecular mechanism predisposing PD rats to hypertriglyceridemia and fat accumulation.

Polylactose Exhibits Prebiotic Activity and Reduces Adiposity and Nonalcoholic Fatty Liver Disease in Rats Fed a High-Fat Diet

Prebiotic dietary fibers change the intestinal microbiome favorably and provide a health benefit to the host. Polylactose is a novel fiber, synthesized by extrusion of lactose. We evaluated its prebiotic activity by determining its fermentability, effect on the microbiota, and effects on adiposity and liver lipids in a diet-induced obesity animal model. Male Wistar rats (4-5 wk old) were fed normal-fat (NF, 25% fat energy) or high-fat (HF, 51% fat energy) diets containing different fibers (6% fiber of interest and 3% cellulose, by weight), including cellulose (NFC and HFC, negative and positive controls, respectively), polylactose (HFPL), lactose matched to residual lactose in the HFPL diet, and 2established prebiotic fibers: polydextrose (HFPD) and fructooligosaccharide (HFFOS). After 10 wk of feeding, organs were harvested and cecal contents collected. HFPL animals had greater cecum weight (3 times greater than HFC) and lower cecal pH (∼1pH unit lower than HFC) than all other groups, suggesting that polylactose is more fermentable than other prebiotic fibers (HFPD, HFFOS; P <0.05). HFPL animals also had increased taxonomic abundance of the probiotic species Bifidobacterium in the cecum relative to all other groups (P <0.05). Epididymal fat pad weight was significantly decreased in the HFPL group (29% decrease compared with HFC) compared with all other HF groups (P <0.05) and did not differ from the NFC group. Liver lipids and cholesterol were reduced in HFPL animals when compared with HFC animals (P <0.05). Polylactose is a fermentable fiber that elicits a beneficial change in the gut microbiota as well as reducing adiposity in rats fed HF diets. These effects of polylactose were greater than those of 2 established prebiotics, fructooligosaccharide and polydextrose, suggesting that polylactose is a potent prebiotic.

Risperidone Exacerbates Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Renal Impairment in Obese Mice.

Risperidone, a second-generation antipsychotic drug used for schizophrenia treatment with less-severe side effects, has recently been applied in major depressive disorder treatment. The mechanism underlying risperidone-associated metabolic disturbances and liver and renal adverse effects warrants further exploration. This research explores how risperidone influences weight, glucose homeostasis, fatty liver scores, liver damage, and renal impairment in high-fat diet (HFD)-administered C57BL6/J mice. Compared with HFD control mice, risperidone-treated obese mice exhibited increases in body, liver, kidney, and retroperitoneal and epididymal fat pad weights, daily food efficiency, serum triglyceride, blood urea nitrogen, creatinine, hepatic triglyceride, and aspartate aminotransferase, and alanine aminotransferase levels, and hepatic fatty acid regulation marker expression. They also exhibited increased insulin resistance and glucose intolerance but decreased serum insulin levels, Akt phosphorylation, and glucose transporter 4 expression. Moreover, their fatty liver score and liver damage demonstrated considerable increases, corresponding to increases in sterol regulatory element-binding protein 1 mRNA, fatty acid-binding protein 4 mRNA, and patatin-like phospholipid domain containing protein 3 expression. Finally, these mice demonstrated renal impairment, associated with decreases in glutathione peroxidase, superoxide dismutase, and catalase levels. In conclusion, long-term administration of risperidone may exacerbate diabetes syndrome, nonalcoholic fatty liver disease, and kidney injury.

Vehicle emissions-exposure alters expression of systemic and tissue-specific components of the renin-angiotensin system and promotes outcomes associated with cardiovascular disease and obesity in wild-type C57BL/6 male mice.

Exposure to air pollution from traffic-generated sources is known to contribute to the etiology of inflammatory diseases, including cardiovascular disease (CVD) and obesity; however, the signaling pathways involved are still under investigation. Dysregulation of the renin-angiotensin system (RAS) can contribute to CVD and alter lipid storage and inflammation in adipose tissue. Our previous exposure studies revealed that traffic-generated emissions increase RAS signaling, further exacerbated by a high-fat diet. Thus, we investigated the hypothesis that exposure to engine emissions increases systemic and local adipocyte RAS signaling, promoting the expression of factors involved in CVD and obesity. Male C57BL/6 mice (6-8 wk old) were fed either a high-fat (HF, n = 16) or low-fat (LF, n = 16) diet, beginning 30d prior to exposures, and then exposed via inhalation to either filtered air (FA, controls) or a mixture of diesel engine + gasoline engine vehicle emissions (MVE: 100 μg PM/m3) via whole-body inhalation for 6 h/d, 7 d/wk, 30d. Endpoints were assessed via immunofluorescence and RT-qPCR. MVE-exposure promoted vascular adhesion factors (VCAM-1, ICAM-1) expression, monocyte/macrophage sequestration, and oxidative stress in the vasculature, associated with increased angiotensin II receptor type 1 (AT1) expression. In the kidney, MVE-exposure promoted the expression of renin, AT1, and AT2 receptors. In adipose tissue, both HF-diet and MVE-exposure mediated increased epididymal fat pad weight and adipocyte hypertrophy, associated with increased angiotensinogen and AT1 receptor expression; however, these outcomes were further exacerbated in the MVE + HF group. MVE-exposure also induced inflammation, monocyte chemoattractant protein (MCP)-1, and leptin, while reducing insulin receptor and glucose transporter, GLUT4, expression in adipose tissue. Our results indicate that MVE-exposure promotes systemic and local adipose RAS signaling, associated with increased expression of factors contributing to CVD and obesity, further exacerbated by HF diet consumption.

Dietary restriction and/or exercise training impairs spermatogenesis in normal rats.

Dietary restriction and/or exercise has been shown to have multiple benefits for health. However, its effects on reproductive health and the mechanisms by which it regulates reproductive function remain unclear. Here, to evaluate its effects on spermatogenesis and sperm function, rats were divided into 4 groups: adlibitum-fed sedentary control, dietary restriction (DR), exercise training (ET), and dietary restriction plus exercise training (DR+ET) groups. Results indicated that body weight, epididymal fat pad weight, and sperm counts were significantly reduced in the DR, ET, and DR+ET groups. Moreover, sperm motility and capacitation-associated protein tyrosine phosphorylation were suppressed in the DR and DR+ET groups, but not the ET group. Microarray analysis revealed that the number of downregulated genes was higher than that of upregulated genes in the DR and/or ET groups. About half of the downregulated genes are common after exercise training and/or diet restriction. Gene ontology analysis showed that downregulated genes in the DR, ET, and DR+ET groups affected spermatogenesis through overlapping pathways, including glucocorticoid, corticosteroid, extracellular structure organization, and estradiol responses. Our findings suggest that diet restriction and/or exercise training may present potential risks to male reproductive dysfunction by disrupting normal gene expression patterns in the testis. Novelty: Dietary restriction and/or exercise can lead to the damage of spermatogenesis as well as sperm maturation. Sperm functional changes are more sensitive to dietary restriction than exercise training. Dietary restriction and exercise impair spermatogenesis through overlapping biological pathways in the testis.

Genome-Wide Association Study in 3,173 Outbred Rats Identifies Multiple Loci for Body Weight, Adiposity, and Fasting Glucose.

Obesity is influenced by genetic and environmental factors. Despite the success of human genome-wide association studies, the specific genes that confer obesity remain largely unknown. The objective of this study was to use outbred rats to identify the genetic loci underlying obesity and related morphometric and metabolic traits. This study measured obesity-relevant traits, including body weight, body length, BMI, fasting glucose, and retroperitoneal, epididymal, and parametrial fat pad weight in 3,173 male and female adult N/NIH heterogeneous stock (HS) rats across three institutions, providing data for the largest rat genome-wide association study to date. Genetic loci were identified using a linear mixed model to account for the complex family relationships of the HS and using covariates to account for differences among the three phenotyping centers. This study identified 32 independent loci, several of which contained only a single gene (e.g., Epha5, Nrg1, Klhl14) or obvious candidate genes (e.g., Adcy3, Prlhr). There were strong phenotypic and genetic correlations among obesity-related traits, and there was extensive pleiotropy at individual loci. This study demonstrates the utility of HS rats for investigating the genetics of obesity-related traits across institutions and identify several candidate genes for future functional testing.

Mirtazapine Reduces Adipocyte Hypertrophy and Increases Glucose Transporter Expression in Obese Mice.

Simple SummaryMirtazapine, a tetracyclic antidepressant, acts through noradrenergic and specific serotonergic systems. Consequently, it was recently applied in major depressive disorder treatment. Moreover, because mirtazapine may have effective glucose control function, its mechanism of action warrants further investigation. In our study, we examined how mirtazapine affects metabolic parameters, insulin profiles, glucose metabolism, and obesity changes in high-fat diet-fed C57BL6/J mice. Our results indicated that compared with untreated mice, mirtazapine-treated obese mice had lower insulin levels, daily food efficiency, body weight, serum triglyceride levels, aspartate aminotransferase levels, liver and epididymal fat pad weight, and fatty acid regulation marker expression. Moreover, the blood glucose levels and area under the curve for glucose levels observed over a 120 min assessment period were lower in the treated mice, but the insulin sensitivity and glucose transporter 4 expression levels were higher in these mice. They also demonstrated a considerable decrease in fatty liver scores and mean fat cell size in the epididymal white adipose tissue, paralleling adenosine monophosphate (AMP)-activated protein kinase expression activation. In conclusion, mirtazapine administration may alleviate type 2 diabetes mellitus with hyperglycemia.Metabolic syndrome is known to engender type 2 diabetes as well as some cardiac, cerebrovascular, and kidney diseases. Mirtazapine—an atypical second-generation antipsychotic drug with less severe side effects than atypical first-generation antipsychotics—may have positive effects on blood glucose levels and obesity. In our executed study, we treated male high-fat diet (HFD)-fed C57BL/6J mice with mirtazapine (10 mg/kg/day mirtazapine) for 4 weeks to understand its antiobesity effects. We noted these mice to exhibit lower insulin levels, daily food efficiency, body weight, serum triglyceride levels, aspartate aminotransferase levels, liver and epididymal fat pad weight, and fatty acid regulation marker expression when compared with their counterparts (i.e., HFD-fed control mice). Furthermore, we determined a considerable drop in fatty liver scores and mean fat cell size in the epididymal white adipose tissue in the treated mice, corresponding to AMP-activated protein kinase expression activation. Notably, the treated mice showed lower glucose tolerance and blood glucose levels, but higher glucose transporter 4 expression. Overall, the aforementioned findings signify that mirtazapine could reduce lipid accumulation and thus prevent HFD-induced increase in body weight. In conclusion, mirtazapine may be useful in body weight control and antihyperglycemia therapy.

Whole Egg Consumption Decreases Cumulative Weight Gain in Diet-Induced Obese Rats

Whole egg (WE) consumption has been demonstrated to attenuate body weight (BW) gain and adiposity in genetic animal models of type 2 diabetes (T2D). This finding was accompanied by increased food consumption. This study aimed to examine the effects of long-term WE intake on BW gain, fat distribution, and food intake in a rat model of diet-induced obesity (DIO). Male Sprague Dawley rats (n=24) were obtained at 5 wk of age and were randomly weight-matched across 1 of 4 dietary intervention groups (6 rats per group): a casein-based diet (CAS), a high-fat high-sucrose CAS diet (HFHS CAS), a whole egg-based diet (EGG), or a high-fat high-sucrose EGG diet (HFHS EGG). All diets provided 20% (w/w) protein and were provided for 33 wk. HFHS diets provided ∼61% of kilocalories from fat and 10% from sucrose. Daily weight gain and food intake were recorded, biochemical parameters were measured via ELISA, and epididymal fat pad weights were recorded at the end of the study. At 33 wk, cumulative BW gain in DIO rats fed HFHS EGG resulted in 23% lower weight gain compared with DIO rats fed HFHS CAS (P <0.0001), but no significant differences in BW gain were observed between the HFHS EGG group and the control EGG and CAS groups (P=0.71 and P=0.61, respectively). Relative food intake (grams per kilogram BW) was 23% lower (P<0.0001) in rats fed HFHS CAS compared with CAS, whereas there was no difference in food intake within the EGG dietary groups. DIO rats fed HFHS EGG exhibited a 22% decrease in epididymal fat weight compared with their counterparts fed the HFHS CAS. Our data demonstrate that consumption of a WE-based diet reduced BW gain and visceral fat in the DIO rat, similar to our previous findings in a genetic rat model with T2D.

Inhibitory Effect of Betanin From Hylocereus ocamponis Against Steatohepatitis in Mice Fed a High-Fat Diet

Betanin is a phytocompound whose effect in steatohepatitis has not yet been tested. Betanin was extracted from the fruits of Hylocereus ocamponis, and its effects were evaluated in a mice model for non-alcoholic fatty liver disease. Six-week-old male BALB/c mice fed with a high-fat diet received 9.6 mg of betanin per day during 40 days. Body, liver, and epididymal fat pad weights and the levels of blood serum total cholesterol, triglycerides, high-density lipoproteins, alanine aminotransferase, blood nitrogen urea, creatinine, and total antioxidant capacity were measured. Hepatosteatosis and inflammatory infiltration were categorized, and the relative cell area of hepatocytes was determined. Betanin inhibited the inflammatory infiltration of the liver ( P = 4.000 × 10−6) and the necrosis of hepatocytes ( P = 9.634 × 10−7); it also produced a predominance of microvesicular steatosis ( P = 9.634 × 10−7), decreased epididymal fat pad weight ( P = 8.250 × 10−4), and increased blood serum total cholesterol ( P = 0.011). Betanin is a promising compound for fatty liver, steatohepatitis, and chronic liver disease.

Discordant Dose-Dependent Metabolic Effects of Eicosapentanoic Acid in Diet-Induced Obese Mice.

Obesity is a widespread epidemic that increases the risk for several metabolic diseases. Despite several beneficial health effects of eicosapentaenoic acid (C20:5n-3, EPA), previous studies have used very high doses of EPA. In this study, dose-dependent effects of EPA on metabolic outcomes were determined in diet-induced obese mice. We used B6 male mice, fed high-fat diet (HF, 45% kcal fat) or HF diet supplemented with 9, 18, and 36 g/kg of EPA-enriched fish oil for 14 weeks. We conducted metabolic phenotyping during the feeding period, and harvested tissues and blood at termination. Only mice fed 36 g/kg of EPA significantly (p < 0.05) lowered body weight, fat content and epididymal fat pad weight, compared to HF. Both 18 and 36 g/kg doses of EPA significantly increased glucose clearance and insulin sensitivity, compared to HF or 9 g/kg of EPA. Locomotor activity was significantly increased with both 18 and 36 g/kg doses of EPA. Interestingly, all doses of EPA compared to HF, significantly increased energy expenditure and oxygen consumption and significantly reduced serum insulin, leptin, and triglycerides levels. These results demonstrate weight- and adiposity-independent metabolic benefits of EPA, at doses comparable to those currently used to treat hypertriglyceridemia.

Threonine, but Not Lysine and Methionine, Reduces Fat Accumulation by Regulating Lipid Metabolism in Obese Mice.

Some amino acids (AAs) have been proven to suppress fat mass and improve insulin sensitivity. However, the impact of important essential AAs, threonine, lysine, and methionine, on obesity has not been clarified. In the present study, after an 8 week period of obesity induction, mice were grouped to receive either a high-fat diet (HFD) or HFD supplemented with lysine, threonine, or methionine (3% in drinking water) for another 10 weeks. The results showed that dietary supplementation with threonine significantly decreased body weight, epididymal and perirenal fat pad weights, serum concentrations of glucose, triacylglycerols, total cholesterol, and LDL-cholesterol compared to the HFD group. HOMA-IR and serum leptin and adiponectin were improved by threonine supplementation. In epididymal adipose tissue, threonine treatment significantly down-regulated the expression levels of lipogenesis and up-regulated expressions of lipolysis compared to the HFD group. Threonine addition stimulated the expression of UCP-1 and related genes in brown adipose tissue. However, lysine or methionine supplementation showed little effect on body weight, WAT weight, serum lipid profiles, and lipid-metabolism-related gene expressions of HFD-fed mice. These findings suggest that threonine inhibited fat mass and improved lipid metabolism of already obese mice, providing a potential agent in treating obesity.