Adipokines In White Adipose Tissue Research Articles

6-Gingerol Ameliorates Adiposity and Inflammation in Adipose Tissue in High Fat Diet-Induced Obese Mice: Association with Regulating of Adipokines.

We investigated the effects of 6-gingerol on adiposity and obesity-induced inflammation by focusing on the regulation of adipogenesis and adipokines in white adipose tissue (WAT) of diet-induced obese mice. C57BL/6 mice were fed a high-fat diet (HFD) containing 0.05% 6-gingerol for 8 weeks. 6-Gingerol supplementation significantly reduced body weight, WAT mass, serum triglyceride, leptin and insulin levels, and HOMA-IR in HFD-fed mice. Additionally, the size of adipocytes in epididymal fat pads was reduced in HFD-fed mice by 6-gingerol supplementation. 6-Gingerol reduced the mRNA and protein levels of adipogenesis-related transcription factors, such as SREBP-1, PPARγ, and C/EBPα in WAT. Furthermore, 6-gingerol suppressed the expression of lipogenesis-related genes, such as fatty acid synthase and CD36 in WAT. Adiponectin expression was significantly increased, whereas inflammatory adipokines (leptin, resistin, TNF-α, MCP-1, and PAI-1) and the macrophage marker F4/80 were significantly reduced in the WAT of HFD-fed mice by 6-gingerol supplementation. In conclusion, 6-gingerol effectively contributed to the alleviation of adiposity and inflammation in WAT, which is associated with the regulation of adipokines in diet-induced obese mice.

Retinoic acid promotes tissue vitamin A status and modulates adipose tissue metabolism of neonatal rats exposed to maternal high-fat diet-induced obesity.

Maternal obesity may compromise the micronutrient status of the offspring. Vitamin A (VA) is an essential micronutrient during neonatal development. Its active metabolite, retinoic acid (RA), is a key regulator of VA homeostasis, which also regulates adipose tissue (AT) development in obese adults. However, its role on VA status and AT metabolism in neonates was unknown and it was determined in the present study. Pregnant Sprague-Dawley rats were randomised to a normal fat diet (NFD) or a high fat diet (HFD). From postnatal day 5 (P5) to P20, half of the HFD pups received oral RA every 3 d (HFDRA group). NFD pups and the remaining HFD pups (HFD group) received placebo. Six hours after dosing on P8, P14 and P20, n 4 pups per group were euthanised for different measures. It was found that total retinol concentration in neonatal liver and lung was significantly lower in the HFD group than the NFD group, while the concentrations were significantly increased in the HFDRA group. The HFD group exhibited significantly higher body weight (BW) gain, AT mass, serum leptin and adiponectin, and gene expression of these adipokines in white adipose tissue compared with the NFD group; these measures were significantly reduced in the HFDRA group. BAT UCP2 and UCP3 gene expression were significantly higher in pups receiving RA. In conclusion, repeated RA treatment during the suckling period improved the tissue VA status of neonates exposed to maternal obesity. RA also exerted a regulatory effect on neonatal obesity development by reducing BW gain and adiposity and modulating AT metabolism.

Selective Modulator of Nuclear Receptor PPARγ with Reduced Adipogenic Potential Ameliorates Experimental Nephrotic Syndrome

Background: Glomerular disease, often manifesting as nephrotic syndrome (NS) with high proteinuria, can be refractory to standard treatment and is typically associated with hypoalbuminemia, hypercholesterolemia and hypercoagulopathy. We hypothesized that the nuclear receptor PPARγ can be selectively modulated using a novel partial agonist, GQ-16, to gain therapeutic advantage over traditional PPARγ agonists (e.g. thiazolidinediones) for the treatment of glomerular disease. Methods: Nephropathy was induced with puromycin amino-nucleoside (PAN) in Wistar rats and treated with Pioglitazone (Pio) or GQ-16. Plasma, serum, and urine chemistries were performed, and kidneys, glomeruli, liver, and white adipose tissue (WAT) were harvested. Lipid accumulation and adipogenic gene expression were measured in adipocytes. Results: PAN-induced proteinuria was significantly reduced with Pio to 64% of PAN-value. It was reduced robustly with GQ-16 to 81% of PAN, which was comparable to controls. While both GQ-16 and Pio restored glomerular Nphs1 and hepatic Pcsk9 expression and reduced hypercholesterolemia, GQ-16 also restored glomerular Nrf2, and reduced hypoalbuminemia and hypercoagulopathy. Furthermore, RNA-seq analysis identified both common and distinct restored glomerular genes downstream of Pio and GQ-16. Pio but not GQ-16 significantly induced aP2 (fatty acid binding protein) in adipocytes and in WAT. Pio induced more lipid accumulation than GQ-16 in differentiated adipocytes. Both, Pio and GQ-16 induced insulin sensitizing adipokines in WAT with varying degrees. Conclusions: Selective modulation of PPARγ by a partial agonist, GQ-16, is more advantageous than pioglitazone in reducing proteinuria and NS associated co-morbidities, while reducing the adipogenic side-effects conferred by traditional PPARγ full agonists.​

Oral Ang-(1-7) treatment improves white adipose tissue remodeling and hypertension in rats with metabolic syndrome

ObjectiveAngiotensin (Ang)-(1-7) has preventive effects on metabolic syndrome (MetS). The aim of this study was to evaluate the therapeutic effect of oral Ang-(1-7) on mean arterial pressure (MAP), insulin resistance (IR), inflammatory process, and remodeling of white adipose tissue (WAT) in rats with established MetS. MethodsRats were subjected to control (CT; AIN-93M) or high-fat (HF) diets for 13 wk to induce MetS and treated with Ang-(1-7) or vehicle (V) for the last 6 wk. At the end of 13 wk, MAP, biochemical and histological parameters, and uncoupling protein (UCP) and inflammatory gene expression were determined by quantitative reverse transcription polymerase chain reaction. ResultsHF-V rats showed increased visceral fat deposition, inflammatory cytokine expression, hyperplasia, and hypertrophy in retroperitoneal (WAT) and brown adipose tissue (BAT). Additionally, the gastrocnemius muscle reduced UCP-3 and increased the UCP-1 expression in BAT. HF-V also elevated levels of plasma insulin, glucose, homeostatic model assessment (HOMA) of IR and HOMA-β, and increased body mass, adiposity, and MAP. Ang-(1-7) treatment in rats with MetS [HF-Ang-(1-7)] reduced WAT area, number of adipocytes, and expression of proinflammatory adipokines in WAT and BAT and increased UCP-3 in gastrocnemius muscle and UCP-1 expression in BAT compared with the HF-V group. These events prevented body mass gain, reduced adiposity, and normalized fasting plasma glucose, insulin levels, HOMA-IR, HOMA-β, and MAP. ConclusionData from the present study demonstrated that oral Ang-(1-7) treatment is effective in restoring biochemical parameters and hypertension in established MetS by improving hypertrophy and hyperplasia in WAT and inflammation in adipose tissue, and regulating metabolic processes in the gastrocnemius muscle and BAT.

LH-21, A Peripheral Cannabinoid Receptor 1 Antagonist, Exerts Favorable Metabolic Modulation Including Antihypertensive Effect in KKAy Mice by Regulating Inflammatory Cytokines and Adipokines on Adipose Tissue.

Patients with obesity are susceptible to hypertension and diabetes. Over-activation of cannabinoid receptor 1 (CB1R) in adipose tissue is proposed in the pathophysiology of metabolic disorders, which led to the metabolic dysfunction of adipose tissue and deregulated production and secretion of adipokines. In the current study, we determined the impact of LH-21, a representative peripheral CB1R antagonist, on the obesity-accompanied hypertension and explored the modulatory action of LH-21 on the adipose tissue in genetically obese and diabetic KKAy mice. 3-week LH-21 treatment significantly decreased blood pressure with a concomitant reduction in body weight, white adipose tissue (WAT) mass, and a slight loss on food intake in KKAy mice. Meanwhile, glucose handling and dyslipidemia were also markedly ameliorated after treatment. Gene expression of pro-inflammatory cytokines in WAT and the aortae were both attenuated apparently by LH-21, as well the mRNA expression of adipokines (lipocalin-2, leptin) in WAT. Concomitant amelioration on the accumulation of lipocalin-2 was observed in both WAT and aortae. In corresponding with this, serum inflammatory related cytokines (tumor necrosis factor α, IL-6, and CXCL1), and lipocalin-2 and leptin were lowered notably. Thus according to current results, it can be concluded that the peripheral CB1R antagonist LH-21 is effective in managing the obesity-accompanied hypertension in KKAy mice. These metabolic benefits are closely associated with the regulation on the production and secretion of inflammatory cytokines and adipokines in the WAT, particularly alleviated circulating lipocalin-2 and its accumulation in aortae.

Metabolically distinct weight loss by 10,12 CLA and caloric restriction highlight the importance of subcutaneous white adipose tissue for glucose homeostasis in mice.

BackgroundWidely used as a weight loss supplement, trans-10,cis-12 conjugated linoleic acid (10,12 CLA) promotes fat loss in obese mice and humans, but has also been associated with insulin resistance.ObjectiveWe therefore sought to directly compare weight loss by 10,12 CLA versus caloric restriction (CR, 15–25%), an acceptable healthy method of weight loss, to determine how 10,12 CLA-mediated weight loss fails to improve glucose metabolism.MethodsObese mice with characteristics of human metabolic syndrome were either supplemented with 10,12 CLA or subjected to CR to promote weight loss. Metabolic endpoints such as energy expenditure, glucose and insulin tolerance testing, and trunk fat distribution were measured.ResultsBy design, 10,12 CLA and CR caused equivalent weight loss, with greater fat loss by 10,12 CLA accompanied by increased energy expenditure, reduced respiratory quotient, increased fat oxidation, accumulation of alternatively activated macrophages, and browning of subcutaneous white adipose tissue (WAT). Moreover, 10,12 CLA-supplemented mice better defended their body temperature against a cold challenge. However, 10,12 CLA concurrently induced the detrimental loss of subcutaneous WAT without reducing visceral WAT, promoted reduced plasma and WAT adipokine levels, worsened hepatic steatosis, and failed to improve glucose metabolism. Obese mice undergoing CR were protected from subcutaneous-specific fat loss, had improved hepatic steatosis, and subsequently showed the expected improvements in WAT adipokines, glucose metabolism and WAT inflammation.ConclusionsThese results suggest that 10,12 CLA mediates the preferential loss of subcutaneous fat that likely contributes to hepatic steatosis and maintained insulin resistance, despite significant weight loss and WAT browning in mice. Collectively, we have shown that weight loss due to 10,12 CLA supplementation or CR results in dramatically different metabolic phenotypes, with the latter promoting a healthier form of weight loss.

Exercise Training Attenuates the Dysregulated Expression of Adipokines and Oxidative Stress in White Adipose Tissue.

Obesity-induced inflammatory changes in white adipose tissue (WAT), which caused dysregulated expression of inflammation-related adipokines involving tumor necrosis factor-α and monocyte chemoattractant protein-1, contribute to the development of insulin resistance. Moreover, current literature reports state that WAT generates reactive oxygen species (ROS), and the enhanced production of ROS in obese WAT has been closely associated with the dysregulated expression of adipokines in WAT. Therefore, the reduction in excess WAT and oxidative stress that results from obesity is thought to be one of the important strategies in preventing and improving lifestyle-related diseases. Exercise training (TR) not only brings about a decrease in WAT mass but also attenuates obesity-induced dysregulated expression of the adipokines in WAT. Furthermore, some reports indicate that TR affects the generation of oxidative stress in WAT. This review outlines the impact of TR on the expression of inflammation-related adipokines and oxidative stress in WAT.

Dietary intervention in obese dams protects male offspring from WAT induction of TRPV4, adiposity, and hyperinsulinemia.

One major risk factor for childhood overweight is maternal obesity. The underlying molecular mechanisms are ill-defined, and effective prevention strategies are missing. Diet-induced obese mouse dams were changed to standard chow during pregnancy and lactation as an intervention against predisposition for obesity and metabolic sequelea in the offspring. Expression of adipokines and TRPV4, a regulator of adipose oxidative metabolism, inflammation, and energy homeostasis, in offspring's white adipose tissue (WAT) was assessed. Pathological effects on offspring's body weight, fat content, and serum insulin were fully reversed in intervention offspring on postnatal day 21. In WAT, a sixfold increase of Trpv4 mRNA expression in offspring consuming high-fat-containing diet was found, which was completely blunted in the intervention group. Simultaneously, WAT adipokine, interleukin-6, and peroxisome proliferator-activated receptor-γ mRNA and UCP1 protein expression were largely returned to control levels in intervention offspring. Improvement of maternal nutrition offers a powerful strategy to improve offspring's metabolic health. Targeting TRPV4-linked aspects of WAT metabolic function during early development might be a promising approach to prevent long-term adverse metabolic effects of maternal high-fat nutrition.

Effect of Electroacupuncture on Inflammation in the Obese Zucker Fatty Rat Model of Metabolic Syndrome

Chronic inflammation is known to be associated with visceral obesity and insulin resistance and is characterized by altered levels of production of adipokines such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-6, leptin, and adiponectin. Metabolic syndrome (MetS) is a major and escalating public health and clinical challenge worldwide, and patients with MetS have an increased risk of developing cardiovascular disease and type 2 diabetes mellitus. Electroacupuncture (EA) was tested as a means of decreasing inflammation in genetically obese Zucker fatty rats, which serve as a model of MetS. Repeated application of EA at the Zhongwan/Guanyuan acupoints decreased serum TNF-α, but produced no significant alterations in serum leptin, adiponectin, or IL-10. EA had no significant effect on the levels of these four adipokines in white adipose tissue. These findings are consistent with the supposition that EA inhibits proliferation and/or infiltration of macrophages into the adipose tissue of obese rats and stimulates the release of IL-10 from the decreased numbers of macrophages present in adipose tissue. Compared with the control animals, no significant change in body weight occurred. The blood glucose (BG) level over a 30-minute interval in Week 2 was relatively the same as that in Week 1, suggesting that EA treatment does not increase the likelihood of developing hyperglycemia.

The Effects of Exercise Training on Obesity-Induced Dysregulated Expression of Adipokines in White Adipose Tissue

Obesity is recognized as a risk factor for lifestyle-related diseases such as type 2 diabetes and cardiovascular disease. White adipose tissue (WAT) is not only a static storage site for energy; it is also a dynamic tissue that is actively involved in metabolic reactions and produces humoral factors, such as leptin and adiponectin, which are collectively referred to as adipokines. Additionally, because there is much evidence that obesity-induced inflammatory changes in WAT, which is caused by dysregulated expression of inflammation-related adipokines involving tumor necrosis factor-α and monocyte chemoattractant protein 1, contribute to the development of insulin resistance, WAT has attracted special attention as an organ that causes diabetes and other lifestyle-related diseases. Exercise training (TR) not only leads to a decrease in WAT mass but also attenuates obesity-induced dysregulated expression of the inflammation-related adipokines in WAT. Therefore, TR is widely used as a tool for preventing and improving lifestyle-related diseases. This review outlines the impact of TR on the expression and secretory response of adipokines in WAT.

Preventive and improvement effects of exercise training and supplement intake in white adipose tissues on obesity and lifestyle-related diseases

Recent increases in the number of obese individuals and individuals suffering from lifestyle-related diseases, such as type 2 diabetes, that accompany obesity have become a serious social problem. White adipose tissue (WAT) is more than a mere organ for storage of energy; it is also a highly active metabolic and endocrine organ that secretes physiologically active substances collectively known as adipokines, including tumor necrosis factor-α and adiponectin. Dysregulated expression of adipokines in WAT that is hypertrophied by obesity has been closely associated with the phenomenon of insulin resistance. Therefore, WAT is currently considered to be one of the tissues that promote lifestyle-related diseases. Reduction of excess WAT that results from obesity is seen as an important strategy in preventing and improving lifestyle-related diseases. This review shows that exercise training as well as intake of supplements, such as polyphenols, is one strategy for this, because this regimen can result in reduction of WAT mass, which affects the expression and secretory response of adipokines.

Nobiletin improves hyperglycemia and insulin resistance in obese diabetic ob/ob mice

Nobiletin is a polymethoxylated flavone found in certain citrus fruits that exhibits various pharmacological effects including anti-inflammatory, antitumor and neuroprotective properties. The present study investigated the effects of nobiletin on insulin sensitivity in obese diabetic ob/ob mice, and the possible mechanisms involved. The ob/ob mice were treated with nobiletin (200mg/kg) for 5 weeks. Nobiletin significantly improved the plasma glucose levels, homeostasis model assessment index, glucose tolerance in an oral glucose tolerance test and plasma adiponectin levels. In white adipose tissue (WAT), nobiletin significantly decreased the mRNA expression levels of inflammatory adipokines such as interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 and increased the mRNA expression levels of adiponectin, peroxisome proliferator-activated receptor (PPAR)-γ and its target genes. At the same time, nobiletin increased the glucose transporter (Glut) 4 expression levels in the whole plasma membrane, and Glut1 and phospho-Akt expression in the whole cell lysates in WAT and muscle. Nobiletin also increased Glut4 protein expression level in the whole cell lysates of the muscle. Taken together, the present results suggest that nobiletin improved the hyperglycemia and insulin resistance in obese diabetic ob/ob mice by regulating expression of Glut1 and Glut4 in WAT and muscle, and expression of adipokines in WAT.

Involvement of adipokines in rimonabant-mediated insulin sensitivity in ob/ob mice

Abstract Objectives It has been recently reported that blockade of type 1 cannabinoid (CB1) receptors by specific antagonists or genetic manipulation alleviates dyslipidaemia, hyperglycaemia and insulin resistance in animal models of obesity and type 2 diabetes. However, the precise role of adipokines in the insulin-sensitising effects of the CB1 antagonist rimonabant is not clear. Methods ob/ob mice were treated with different doses of rimonabant and then subjected to an oral glucose tolerance test. The expression of different adipokines in white adipose tissue was analysed by quantitative real-time PCR. Key findings Rimonabant (30 mg/kg) significantly inhibited body weight and fat pad weight gain (P < 0.05) and improved glucose tolerance. Gene expression analysis indicated that tumour necrosis factor-α, visfatin and retinol binding protein-4 were downregulated in the adipose tissue of ob/ob mice treated with rimonabant compared with controls, whereas adiponectin was significantly upregulated. Conclusions Rimonabant-mediated alteration of adipokines in white adipose tissues may play a role in improving insulin sensitivity in obese animals.

Involvement of adipokines in rimonabant-mediated insulin sensitivity in <I>ob/ob</I> mice

It has been recently reported that blockade of type 1 cannabinoid (CB1) receptors by specific antagonists or genetic manipulation alleviates dyslipidaemia, hyperglycaemia and insulin resistance in animal models of obesity and type 2 diabetes. However, the precise role of adipokines in the insulin-sensitising effects of the CB1 antagonist rimonabant is not clear. ob/ob mice were treated with different doses of rimonabant and then subjected to an oral glucose tolerance test. The expression of different adipokines in white adipose tissue was analysed by quantitative real-time PCR. Rimonabant (30 mg/kg) significantly inhibited body weight and fat pad weight gain (P < 0.05) and improved glucose tolerance. Gene expression analysis indicated that tumour necrosis factor-alpha, visfatin and retinol binding protein-4 were downregulated in the adipose tissue of ob/ob mice treated with rimonabant compared with controls, whereas adiponectin was significantly upregulated. Rimonabant-mediated alteration of adipokines in white adipose tissues may play a role in improving insulin sensitivity in obese animals.

Antioxidative Effects of a New Lychee Fruit-Derived Polyphenol Mixture, Oligonol, Converted into a Low-Molecular Form in Adipocytes

In this study we investigated the antioxidative effects of Oligonol (Amino Up Chemical Co., Ltd., Sapporo, Japan), a new polyphenol, in adipocytes. The levels of reactive oxygen species (ROS) and the expression of adipokine genes decreased in HW mouse white adipocytes upon treatment with Oligonol as compared to control cells. The transcriptional activity of nuclear factor-kappaB (NF-kappaB) and the activation of extracellular signal-regulated kinase (ERK) 1/2 were also down-regulated by Oligonol. In addition, when C57BL/6J mice were fed a high fat diet (HFD) for 5 weeks, the levels of epididymal white adipose tissue (WAT) mass and lipid peroxidation in WAT both increased, but Oligonol intake clearly inhibited such HFD-induced increases. Furthermore, dysregulated expression of genes for adipokines in WAT of mice fed solely a HFD was attenuated by Oligonol intake. These results suggest that Oligonol has antioxidative effects and that it attenuates HFD-induced dysregulated expression of genes for adipokines in adipocytes.