Genes In Epididymal Adipose Tissue Research Articles

Receptor-interacting protein 1 and 3 kinase activity are required for high-fat diet induced liver injury in mice.

The RIP1-RIP3-MLKL-mediated cell death pathway is associated with progression of non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH). Previous work identified a critical role for MLKL, the key effector regulating necroptosis, but not RIP3, in mediating high fat diet-induced liver injury in mice. RIP1 and RIP3 have active N-terminus kinase domains essential for activation of MLKL and subsequent necroptosis. However, little is known regarding domain-specific roles of RIP1/RIP3 kinase in liver diseases. Here, we hypothesized that RIP1/RIP3 kinase activity are required for the development of high fat diet-induced liver injury. Rip1K45A/K45A and Rip3K51A/K51A kinase-dead mice on a C57BL/6J background and their littermate controls (WT) were allowed free access to a diet high in fat, fructose and cholesterol (FFC diet) or chow diet. Both Rip1K45A/K45A and Rip3K51A/K51A mice were protected against FFC diet-induced steatosis, hepatocyte injury and expression of hepatic inflammatory cytokines and chemokines. FFC diet increased phosphorylation and oligomerization of MLKL and hepatocyte death in livers of WT, but not in Rip3K51A/K51A, mice. Consistent with in vivo data, RIP3 kinase deficiency in primary hepatocytes prevented palmitic acid-induced translocation of MLKL to the cell surface and cytotoxicity. Additionally, loss of Rip1 or Rip3 kinase suppressed FFC diet-mediated formation of crown-like structures (indicators of dead adipocytes) and expression of mRNA for inflammatory response genes in epididymal adipose tissue. Moreover, FFC diet increased expression of multiple adipokines, including leptin and plasminogen activator inhibitor 1, in WT mice, which was abrogated by Rip3 kinase deficiency. The current data indicate that both RIP1 and RIP3 kinase activity contribute to FFC diet-induced liver injury. This effect of RIP1 and RIP3 kinase deficiency on injury is consistent with the protection of Mlkl-/- mice from high fat diet-induced liver injury, but not the reported lack of protection in Rip3-/- mice. Taken together with previous reports, our data suggest that other domains of RIP3 likely counteract the effect of RIP3 kinase in response to high fat diets.

Lactobacillus paracasei L9 ameliorated obesity-associated metabolic parameters and relevant gut microbiota in mice fed a high-fat diet

The purpose of the present study was to determine whether Lactobacillus paracasei L9 (L9) supplementation prevents diet-induced obesity in C57BL/6J mice. Four-week-old mice were fed a high-fat diet (HFD) for 12 weeks and then supplemented with or without L9 for another 12 weeks. Weight gain, white adipose tissue weight, plasma lipid levels of total cholesterol, triglyceride, and low-density lipoprotein-cholesterol were significantly increased in the HFD group compared with those in the control group and were decreased by L9 treatment. The fat deposits in the liver and epididymal adipose tissue were increased in the HFD group compared with the normal chow diet group and decreased by L9 treatment. Reverse transcriptase-polymerase chain reaction analyses revealed that L9 suppressed pro-inflammatory cytokine and lipid synthesis–related genes in epididymal adipose tissue. This study used Illumina Miseq sequencing to explore alterations of the gut microbiome. L9 ameliorated HFD-induced structural dysbiosis and gut bacteria that were positively related with obesity phenotypes were obviously decreased. Altogether, the findings indicate that administration of L9 ameliorates HFD-induced hyperlipidemia and lipid accumulation in liver and inflammation associated with intestinal dysbiosis in obese mice. These findings suggest that L9 supplementation may provide a natural alternative to attenuate obesity.

Comparative study on short and long-term intervention impacts of six Chinese herbs with cold or heat property on lipid and energy metabolism in mice

This study selected three typical Chinese herbs with cold property(Rhei Radix et Rhizoma, Scutellariae Radix, and Coptidis Rhizoma) and another three with heat property(Cinnamomi Cortex, Zingiberris Rhizoma, and Aconiti Lateralis Radix Praeparata) to observe their regulatory effects on metabolism in animal organism, especially on lipid and energy metabolism in mice after a short-(7 d) and long-term(35 d) intervention. The mRNA expression levels of lipid metabolism genes in epididymal adipose tissue and liver were determined by real-time PCR. The oxygen consumption, carbon dioxide production, and energy consumption were detected by metabolic system. After the short-term intervention, the Chinese herbs with heat property significantly reduced epididymal adipose tissue index and elevated the expression levels of acetyl-CoA carboxylase(ACC), lipoprotein lipase(LPL), and carnitine-palmityl transferase 1(CPT-1) in liver and epididymal adipose tissues. However, those with cold property promoted the expression of above-mentioned genes in epididymal adipose tissue. After the long-term intervention, cold and heat Chinese herbs had no significant effect on epididymal adipose tissue index of animals, while cold Chinese herbs could increase carbon dioxide production and energy consumption and reduce activity. These findings demonstrated that the short-term intervention effects of cold and heat Chinese herbs on animal metabolism were significantly stronger than the long-term intervention effects. Specifically, the short-term intervention with cold Chinese herbs enhanced the lipid metabolism in epididymal adipose tissue, while the heat Chinese herbs promoted lipid metabolism in epididymal adipose tissue and liver. The long-term intervention with cold and heat Chinese herbs resulted in no obvious change in lipid level, but long-term intervention with cold Chinese herbs accelerated energy consumption of the body. This study preliminarily observed the effects of cold and heat Chinese herbs on normal animal physiology from lipid and energy metabolism, which would provide reference for explaining the biological basis of Chinese herbs with cold or heat property based on biological response.

Long-term nitrate administration increases expression of browning genes in epididymal adipose tissue of male type 2 diabetic rats

Expression of browning genes are lower in both humans and animals with type 2 diabetes (T2D). This study aims at determining effects of long-term nitrate administration on protein and mRNA levels of uncoupling protein 1 (UCP1), peroxisome proliferator activated receptor gamma (PPAR-γ), and PPAR-γ coactivator 1 alpha (PGC1-α) in epididymal adipose tissue (eAT) of rats with T2D. Male Wistar rats were divided into 4 groups (n = 6/group): Control, diabetes, control + nitrate (CN), and diabetes + nitrate (DN). T2D was induced using high fat diet combined with a low-dose of streptozotocin (30 mg/kg body weight). Sodium nitrate was administrated at a dose of 100 mg/L for 6 months in nitrate-treated rats. Fasting serum glucose and insulin concentrations were measured at months 0 (i.e. at start of the protocol), 3, and 6. At month 6, protein and mRNA levels of UCP1, PPAR-γ, and PGC1-α were measured in eAT samples. In addition, tissue concentration of cyclic guanosine monophosphate (cGMP) was measured and histological analyses were done at month 6. In rats with T2D, 6-month administration of nitrate decreased serum glucose and insulin concentrations by 13% and 23%, respectively and increased cGMP level by 85%. Rats with T2D had lower mRNA and protein levels of PPAR-γ (62%, P < 0.0001 and 18%, P = 0.0472), PGC1-α (49%, P = 0.0019 and 21%, P = 0.0482), and UCP1 (35%, P = 0.0613 and 30%, P = 0.0031) in eAT; 6-month nitrate administration restored these decreased levels to near control values. In addition, nitrate increased adipocyte density by 193% and decreased adipocyte area by 53% in rats with T2D. In conclusion, long-term low-dose nitrate administration increased mRNA and protein expressions of browning genes in white adipose tissue of male rats with T2D; these findings partly explain favorable metabolic effects of nitrate administration in diabetes.

Amelioration of Mugwort on the Obesity and Dyslipidemia Induced by High-Fat Diet

Anti-obesity effects of Mugwort were evaluated in high fat diet-induced obesity mice models through determining physical changes and gene expression levels. High fat diet (HFD) models fed with 1% or 3% Mugwort had significantly lower body weight gain and food intake than HFD group (p<0.05). Especially, body weight gain and food intake of 3% Mugwort fed groups significantly decreased by 48.5% and 25.8%, respectively, compared to HFD group. In addition, parameters in plasma including LDL levels, concentration of plasma triglyceride and total cholesterol as well as histological changes in the liver were reduced in Mugwort supplemented groups compared to the HFD. Addition of Mugwort decreased the gene expression levels of epididymal adipose tissue genes including ACC, GPDH, and PPARγ. Therefore, Mugwort supplementation may participate in regulating plasma and hepatic steatosis as well as down-regulating adipogenic target gene expression.

Effects of Japanese diet in combination with exercise on visceral fat accumulation.

In our previous study, we showed that among Japanese diets from different time periods, the 1975 Japanese diet has the greatest health benefits and is the most effective to prevent obesity. In addition, exercise is also effective to reduce obesity. Therefore, we conducted a human clinical trial combining the 1975 Japanese diet and exercise and, as a result, found a reduction in body weight, visceral fat, and serum lipids. However, the mechanism of this phenomenon was not determined. Therefore, in this study, we examined this mechanism in mice using a diet that was similar to that used in the human trial. The modern and 1975 Japanese diets were cooked, lyophilized, powdered, and fed freely to 5 wk old male C57 BL/6 J mice for 8 wk. In addition, the mice exercised on a treadmill. Total white adipose tissue weight decreased significantly due to the interaction between the 1975 Japanese diet and exercise. A histologic examination revealed that the hypertrophy of adipocytes was suppressed. To clarify this mechanism, the mRNA levels for lipid metabolism-related genes in epididymal adipose tissue were measured, and the mRNA level of hormone sensitive lipase (Hsl), which is related to lipolysis, was found to be significantly increased after intake of the 1975 Japanese diet combined with exercise. In the gut microbiota analysis, the Bacteroidetes to Firmicutes ratio, which is decreased in obese people, was increased by the 1975 Japanese diet and exercise. At the genus level, there was an increase in butyrate-producing bacteria as a result of the 1975 Japanese diet intake and exercise. A combination of the 1975 Japanese diet and exercise increased lipolysis in white adipose tissue and increased butyrate-producing bacteria in gut microbiota, and thereby suppressed fat accumulation.

Mitochondria‐Generated Acetyl‐CoA Regulates Gene Expression in Hepatic Lipid Synthesis

During the absorptive state the liver stores excess glucose as glycogen and synthesizes fatty acids for triglyceride synthesis for export as very low density lipoproteins. For de novo synthesis of fatty acids from glucose, the mitochondrial pyruvate dehydrogenase complex (PDC) plays a gatekeeper's role for generation of the carbon‐flux as acetyl‐CoA. We have shown previously that there was no incorporation of radioactive glucose‐carbon into newly synthesized fatty acids in livers from liver‐specific PDC‐deficient male mice (L‐PDHKO) due to the null mutation of the Pdha1 gene. In the present study, although the postnatal growth of L‐PDHKO mice was largely unaltered, they developed hyperinsulinemia with lower blood glucose levels in the fed state. Serum and liver lipid triglyceride and cholesterol levels remained unaltered in L‐PDHKO mice. To determine the effect of liver‐specific PDC deficiency on lipid and glucose metabolism, we investigated expression of several key genes as well as their upstream regulators in lipid and glucose metabolism. Interestingly, there was significant downregulation of expression of several key genes (such as ATP‐citrate lyase, acetyl‐CoA carboxylase) in the de novo fatty acid synthesis pathway and their upstream regulators (such as LXR, SREBP1, ChREBP). Downregulation of several genes in the metabolism of glucose (glucose‐6‐phosphate dehydrogenase, pyruvate kinase, phosphoenolpyruvate carboxykinase) and fatty acid oxidation (fatty acid transporter, carnitine‐palmitoyl‐CoA transferase‐1) were also observed in livers of L‐PDHKO mice. Interestingly, there was upregulation of lipogenic genes in epididymal adipose tissue from L‐PDHKO mice. Although, the total hepatic acetyl‐CoA content remained unaltered in these mice, modified acetylation profiles of several proteins in the nucleo‐cytoplasmic compartment (including increased level of acetylated histone3lysine9, H3K9) in livers of L‐PDHKO mice suggest an important role of mitochondria‐generated acetyl‐CoA from glucose‐derived pyruvate by PDC in gene expression in hepatic lipid metabolism. This finding has important implications for regulation of hepatic lipid biosynthesis in obesity, type 2 diabetes and non‐alcoholic fatty liver disease.Support or Funding Information(Supported in part by NIH Grant DK20478 and Department Fund, The Research Foundation of The State University of New York.)

Deletion of SIRT1 in myeloid cells impairs glucose metabolism with enhancing inflammatory response to adipose tissue hypoxia.

Chronic inflammation is a pathophysiology of insulin resistance in metabolic diseases, such as obesity and type 2 diabetes. Adipose tissue macrophages (ATMs) play important roles in this inflammatory process. SIRT1 is implicated in the regulation of glucose metabolism in some metabolic tissues, such as liver or skeletal muscle. This study was performed to investigate whether SIRT1 in macrophages played any roles in the regulation of inflammation and glucose metabolism. Myeloid cell-specific SIRT1-knockout mice were originally generated and analyzed under chow-fed and high-fat-fed conditions. Myeloid cell-specific SIRT1 deletion impaired insulin sensitivity and glucose tolerance assessed by the glucose- or insulin-tolerance test, which was associated with the enhanced expression of inflammation-related genes in epididymal adipose tissue of high-fat-fed mice. Interestingly, the M1 ATMs from the SIRT1-knockout mice showed more hypoxic and inflammatory phenotypes than those from control mice. The expressions of some inflammatory genes, such as Il1b and Nos2, which were induced by in vitro hypoxia treatment, were further enhanced by SIRT1 deletion along with the increased acetylation of HIF-1α in cultured macrophages. These results suggest that deletion of SIRT1 in myeloid cells impairs glucose metabolism by enhancing the hypoxia and inflammatory responses in ATMs, thereby possibly representing a novel therapeutic target for metabolic diseases, such as type 2 diabetes.

Fucoidan Prevents High‐Fat Diet‐Induced Obesity in Animals by Suppression of Fat Accumulation

This study examines the antiobesity effects of fucoidan in an animal model of diet-induced obesity. Mice were fed a standard diet or high-fat diet (HFD) for 5 weeks. After that, the mice were divided into four experimental groups, with 10 mice per group, including a standard diet group, HFD group, HFD containing 1% fucoidan (HFD + FUCO 1%) group and HFD containing 2% fucoidan (HFD + FUCO 2%) group. The fucoidan supplementation group had significantly decreased body-weight gain, food efficiency ratio and relative liver and epididymal fat mass compared with the HFD group. The mice supplemented with fucoidan showed significantly reduced triglyceride, total cholesterol and low-density lipoprotein levels in the plasma. Liver steatosis induced by the HFD improved in the fucoidan-supplemented group. Furthermore, fucoidan affected the down-regulation expression patterns of epididymal adipose tissue genes such as peroxisome proliferator-activated receptor γ, adipose-specific fatty acid binding protein and acetyl CoA carboxylase. Therefore, fucoidan may be considered for use in improving obesity.

Effect of garlic on high fat induced obesity

The present study was performed to examine the effects of garlic on obesity and blood lipid profiles in high-fat induced obesity mice model, and to elucidate the molecular mechanisms responsible for such effect. C57BL/6 mice were fed a standard diet (STD) or high-fat diet (HFD) for 5 weeks to induce obesity. Mice were then randomly divided into four groups with 10 mice per group, and fed experimental diet for 4 weeks; STD group, HFD group, HFD containing 2% or 4% garlic group (HFD + G2 or HFD + G4, respectively). Administration of garlic significantly reduced HFD-induced body weight, epididymal fat accumulation, hyperlipidemia and hypercholesterolemia. Consequently, the atherogenic indexes were reduced by 83% and 91%, respectively, in 2% and 4% garlic supplemented group. Liver steatosis induced by HFD was ameliorated by garlic supplementation. Furthermore, garlic affected the down regulation of expression patterns of epididymal adipose tissue genes such as peroxisome proliferator-activated receptor γ (PPARγ), acetyl CoA carboxylase (ACC), adipose specific fatty acid binding protein (aP2), and glycerol-3-phosphate dehydrogenase (GPDH). These results suggest that garlic may have a potential benefit in preventing obesity.

Food restriction improves glucose and lipid metabolism through Sirt1 expression: A study using a new rat model with obesity and severe hypertension

Aims To determine the effects of food restriction (FR) on the expression of Sirt1 and its down-stream factors related to lipid and glucose metabolism in obese and hypertensive rats (SHRSP/IDmcr- fa), as a model of human metabolic syndrome. Main methods Male, 10-week-old SHRSP/IDmcr- fa rats were treated with 85% FR for 2 weeks. Metabolic parameters, serum adipocytokines and distribution of serum adiponectin multimers were investigated. Sirt1 expression was determined in epididymal adipose tissue, liver and skeletal muscle. We also determined the expression of PPARα, γ and other adipocyte-related genes in epididymal adipose tissue, and glucose transporters (GLUT2 and GLUT4) in the liver and skeletal muscle. Key findings FR improved the general conditions as well as blood chemistry of SHRSP/IDmcr- fa rats. In the epididymal adipose tissue of the FR rats, Sirt1 expression was enhanced, as was adiponectin, whereas leptin was downregulation, findings that were paralleled by the serum protein levels. Furthermore, the serum ratio of high to total adiponectin was increased in the FR group. The mRNA expression of Sirt1 was upregulated in the adipose tissue in the FR group. Sirt1 mRNA expression was downregulated, while PPARα and GLUT2 expression was enhanced in the liver. No differences were found in terms of Sirt1, PPAR or GLUT4 expression in skeletal muscle. Significance These results indicate that FR corrects adipokine dysfunction by activating PPARγ via Sirt1 in adipose tissue. Furthermore, glucose and lipid metabolism are activated by upregulation of GLUT2 via the activation of PPARα in the liver.

Adipocyte Apoptosis, a Link between Obesity, Insulin Resistance, and Hepatic Steatosis

Adipocyte death has been reported in both obese humans and rodents. However, its role in metabolic disorders, including insulin resistance, hepatic steatosis, and inflammation associated with obesity has not been studied. We now show using real-time reverse transcription-PCR arrays that adipose tissue of obese mice display a pro-apoptotic phenotype. Moreover, caspase activation and adipocyte apoptosis were markedly increased in adipose tissue from both mice with diet-induced obesity and obese humans. These changes were associated with activation of both the extrinsic, death receptor-mediated, and intrinsic, mitochondrial-mediated pathways of apoptosis. Genetic inactivation of Bid, a key pro-apoptotic molecule that serves as a link between these two cell death pathways, significantly reduced caspase activation, adipocyte apoptosis, prevented adipose tissue macrophage infiltration, and protected against the development of systemic insulin resistance and hepatic steatosis independent of body weight. These data strongly suggest that adipocyte apoptosis is a key initial event that contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis associated with obesity in both mice and humans. Inhibition of adipocyte apoptosis may be a new therapeutic strategy for the treatment of obesity-associated metabolic complications.

Perilla leaf extract ameliorates obesity and dyslipidemia induced by high‐fat diet

The objective of this study was to evaluate the antiobesity effect of perilla leaf extract (PLE) in animal models of high fat diet-induced obesity. C57BL/6J mice were fed a standard diet (STD) or high fat diet (HFD) for 5 weeks to induce obesity. The experimental groups were four groups with 10 mice per group and fed for 4 weeks: a STD group, a HFD group, a HFD containing 1% PLE (HFD+PLE 1%) group and a HFD containing 3% PLE (HFD+PLE 3%) group. The PLE supplementation significantly decreased body weight gain, food efficiency ratio, and relative liver and epididymal fat mass compared with those of the HFD group. Also, triglyceride, total cholesterol and LDL levels in the plasma were significantly reduced by PLE supplementation compared with the HFD group. Histological changes in the liver of the PLE supplemented group showed an inhibition of steatosis induced by HFD. Furthermore, PLE reversed the HFD induced changes in the expression patterns of epididymal adipose tissue genes: acetyl CoA carboxylase (ACC), glycerol-3-phosphate dehydrogenase (GPDH) and peroxisome proliferator-activated receptor gamma (PPARgamma). These results suggest that the PLE supplement suppressed body weight gain and improved the blood lipid profiling, in part by down-regulating adipogenic transcription factor and other specific target genes.

Garcinia cambogiaExtract Ameliorates Visceral Adiposity in C57BL/6J Mice Fed on a High-Fat Diet

The aim of present study is to evaluate the effects of Garcinia cambogia on the mRNA levels of the various genes involved in adipogenesis, as well as on body weight gain, visceral fat accumulation, and other biochemical markers of obesity in obesity-prone C57BL/6J mice. Consumption of the Garcinia cambogia extract effectively lowered the body weight gain, visceral fat accumulation, blood and hepatic lipid concentrations, and plasma insulin and leptin levels in a high-fat diet (HFD)-induced obesity mouse model. The Garcinia cambogia extract reversed the HFD-induced changes in the expression pattern of such epididymal adipose tissue genes as adipocyte protein aP2 (aP2), sterol regulatory element-binding factor 1c (SREBP1c), peroxisome proliferator-activated receptor gamma2 (PPARgamma2), and CCAT/enhancer-binding protein alpha (C/EBPalpha). These findings suggest that the Garcinia cambogia extract ameliorated HFD-induced obesity, probably by modulating multiple genes associated with adipogenesis, such as aP2, SREBP1c, PPARgamma2, and C/EBPalpha in the visceral fat tissue of mice.

High‐fat Diet Alters PP2A, TC10, and CIP4 Expression in Visceral Adipose Tissue of Rats

The aim of this study was to investigate a possible link between high-fat diet (HFD)-induced obesity and the expression of protein phosphatase 2A (PP2A) and Cdc42-interacting protein 4 (CIP4) proteins, potential downstream components of the IRS/PI3K/AKT and CAP/Cbl/TC10 pathway, respectively, in the visceral adipose tissue. Twenty male Sprague-Dawley rats were randomly divided into two groups and were given either HFD or the normal diet (ND) for 8 weeks. The HFD-induced changes in the expression of the epididymal adipose tissue genes involved in the insulin-signaling pathways were evaluated using real-time reverse-transcription PCR and western blot analysis. The exposure of rats to HFD for 8 weeks resulted in a significant increase in the expression of PP2A at both the transcriptional and translational levels, along with a marked reduction in the levels of phosphorylated AKT and insulin receptor substrate-1 (IRS-1) in the cytosol of visceral adipocytes, compared with the ND rats. Besides, there were significant HFD-induced decreases in the mRNA and protein levels of CIP4 and TC10 in the adipose tissue of rats. These data suggest that HFD might have a relevance to insulin resistance by increasing the expression of PP2A, an inhibitor of AKT activity in the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, and also by suppressing the expression of TC10 and CIP4, downstream effectors of the Cbl/CAP/TC10 insulin-signaling cascade in the visceral adipose tissue.

Ilex paraguariensis extract ameliorates obesity induced by high-fat diet: Potential role of AMPK in the visceral adipose tissue

The aim of present study was to investigate the anti-obesity effect of Ilex paraguariensis extract and its molecular mechanism in rats rendered obese by a high-fat diet (HFD). I. paraguariensis extract supplementation significantly lowered body weight, visceral fat-pad weights, blood and hepatic lipid, glucose, insulin, and leptin levels of rats administered HFD. Feeding I. paraguariensis extract reversed the HFD-induced downregulation of the epididymal adipose tissue genes implicated in adipogenesis or thermogenesis, such as peroxisome proliferators’ activated receptor γ2, adipocyte fatty acid binding protein, sterol-regulatory-element-binding protein-1c, fatty acid synthase, HMG-CoA reductase, uncoupling protein 2, and uncoupling protein 3. Dietary supplementation with I. paraguariensis extract protected rats from the HFD-induced decreases in the phospho-AMP-activated protein kinase (AMPK)/AMPK and phospho-acetyl-CoA carboxylase (ACC)/ACC protein ratio related to fatty acid oxidation in the edipidymal adipose tissue. The present study reports that the I. paraguariensis extract can have a protective effect against a HFD-induced obesity in rats through an enhanced expression of uncoupling proteins and elevated AMPK phosphorylation in the visceral adipose tissue.

Anti-obesity Effects of Juniperus chinensis Extract Are Associated with Increased AMP-Activated Protein Kinase Expression and Phosphorylation in the Visceral Adipose Tissue of Rats

This study evaluates the protective effect of Juniperus chinensis hot water extract (JCE) against high-fat-diet (HFD)-induced obesity and its molecular mechanisms in the visceral adipose tissue of rats. JCE supplementation significantly lowered body weight gain, visceral fat-pad weights, blood lipid levels, and blood insulin and leptin levels of rats rendered obese by an HFD. Feeding with JCE significantly reversed the HFD-induced down-regulation of the epididymal adipose tissue genes implicated in adipogenesis, such as the peroxisome proliferator-activated receptors gamma2 (PPARgamma2), adipocyte protein 2 (aP2), sterol regulatory element binding protein 1c (SREBP1c), fatty acid synthase (FAS), and HMG-CoA reductase (HMGR), as well as those involved in uncoupled respiration, such as the uncoupling protein 2 (UCP2) and uncoupling protein 3 (UCP3). Dietary supplementation with JCE also reversed the HFD-induced decreases in the AMP-activated protein kinase (AMPK) and the acetyl-CoA carboxylase 2 (ACC2) expressions at both the mRNA and protein levels and restored the HFD-induced inhibitions in the AMPK and ACC2 phosphorylation, which are related to fatty acid beta-oxidation, in the epididymal adipose tissue. This study reports, for the first time, that the JCE can have an anti-obesity effect in a rodent model with HFD-induced obesity through an enhanced gene transcription of the uncoupling protein as well as an elevated AMPK protein expression and phosphorylation in the visceral adipose tissue.

Interaction of Fish Oil and Conjugated Linoleic Acid in Affecting Hepatic Activity of Lipogenic Enzymes and Gene Expression in Liver and Adipose Tissue

The interaction of dietary fish oil and conjugated linoleic acid (CLA) in affecting the activity of hepatic lipogenic enzymes and gene expression in liver and adipose tissue was examined in mice. A diet containing 1.0% CLA, mainly composed of 9cis,11trans- and 10trans,12cis-octadecadienoic acids at equivalent amounts, greatly decreased adipose tissue weight and serum concentrations of leptin and adiponectin and was accompanied by a downregulation of the expression of various adipocyte-abundant genes in epididymal adipose tissue. However, CLA increased the serum insulin concentration fourfold, and it caused hepatomegaly, with huge increases in the triacylglycerol level and the activity and mRNA levels of hepatic lipogenic enzymes. Different amounts (1.5, 3, and 6%) of fish oil added to CLA-containing diets dose-dependently downregulated parameters of lipogenesis and were accompanied by a parallel decrease in the triacylglycerol level in the liver. The supplementation of CLA-containing diets with fish oil was also associated with an increase in fat pad mass and mRNA levels of many adipocyte-abundant genes in epididymal adipose tissue along with a normalization of serum concentrations of leptin and adiponectin in a dose-dependent manner. However, in mice fed a diet containing 1.5% fish oil and CLA in whom fat pad mass was still low and comparable to that in the animals fed CLA alone, the serum insulin concentration greatly exceeded (twofold) the value observed in mice fed CLA alone, indicating an aggravation of insulin resistance. This hyperinsulinemia was ameliorated with increasing amounts of fish oil in the diets. Apparently, many of the physiological effects of CLA can be reversed by fish oil.