Dataset Information

Resveratrol reduces the inflammatory response in adipose tissue and improves adipose insulin signaling in high-fat diet-fed mice.

ABSTRACT:

Background

Obesity-induced glucose metabolism disorder is associated with chronic, low-grade, systemic inflammation and is considered a risk factor for diabetes and metabolic syndrome. Resveratrol (RES), a natural anti-inflammatory compound, is observed to improve glucose tolerance and insulin sensitivity in obese rodents and humans. This study aimed to test the effects of RES administration on insulin signaling and the inflammatory response in visceral white adipose tissue (WAT) caused by a high-fat diet (HFD) in mice.

Methods

A total of 40 wild-type C57BL/6 male mice were divided into four groups (10 in each group): the standard chow diet (STD) group was fed a STD; the HFD group was fed a HFD; and the HFD-RES/L and HFD-RES/H groups were fed a HFD plus RES (200 and 400 mg/kg/day, respectively). The L and H in RES/L and RES/H stand for low and high, respectively. Glucose tolerance, insulin sensitivity, circulating inflammatory biomarkers and lipid profile were determined. Quantitative PCR and Western blot were used to determine the expression of CC-chemokine receptor 2 (CCR2), other inflammation markers, glucose transporter 4 (GLUT4), insulin receptor substrate 1 (IRS-1) and pAkt/Akt and to assess targets of interest involving glucose metabolism and inflammation in visceral WAT.

Results

HFD increased the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol and proinflammatory cytokines in serum, decreased the high-density lipoprotein cholesterol level in serum, and induced insulin resistance and WAT inflammation in mice. However, RES treatment alleviated insulin resistance, increased the expressions of pAkt, GLUT4 and IRS-1 in WAT, and decreased serum proinflammatory cytokine levels, macrophage infiltration and CCR2 expression in WAT.

Conclusion

Our results indicated that WAT CCR2 may play a vital role in macrophage infiltration and the inflammatory response during the development of insulin resistance in HFD-induced obesity. These data suggested that administration of RES offers protection against abnormal glucose metabolism and inflammatory adaptations in visceral WAT in mice with HFD-induced obesity.

SUBMITTER: Ding S

PROVIDER: S-EPMC6027658 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Resveratrol reduces the inflammatory response in adipose tissue and improves adipose insulin signaling in high-fat diet-fed mice.

Ding Shibin S Jiang Jinjin J Wang Zhe Z Zhang Guofu G Yin Jianli J Wang Xiaoya X Wang Sui S Yu Zengli Z

PeerJ 20180629

<h4>Background</h4>Obesity-induced glucose metabolism disorder is associated with chronic, low-grade, systemic inflammation and is considered a risk factor for diabetes and metabolic syndrome. Resveratrol (RES), a natural anti-inflammatory compound, is observed to improve glucose tolerance and insulin sensitivity in obese rodents and humans. This study aimed to test the effects of RES administration on insulin signaling and the inflammatory response in visceral white adipose tissue (WAT) caused ...[more]

PMID: 29967759

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Project description:Obesity is associated with a chronic, low-grade, systemic inflammation that may contribute to the development of insulin resistance and type 2 diabetes. Resveratrol, a natural compound with anti-inflammatory properties, is shown to improve glucose tolerance and insulin sensitivity in obese mice and humans. Here we tested the effect of a 2-year resveratrol administration on the pro-inflammatory profile and insulin resistance caused by a high-fat, high-sugar (HFS) diet in white adipose tissue (WAT) from rhesus monkeys. Eighty mg/day of resveratrol for 12-month followed by 480 mg/day for the second year decreased adipocyte size, increased sirtuin 1 expression, decreased NF-kB activation and improved insulin sensitivity in visceral but not subcutaneous WAT from HFS-fed animals. These effects were reproduced in 3T3-L1 adipocytes cultured in media supplemented with serum from monkeys fed HFS +/- resveratrol diets. In conclusion, chronic administration of resveratrol exerts beneficial metabolic and inflammatory adaptations in visceral WAT from diet-induced obese monkeys. Twenty-four adult (7-13 years old) male rhesus monkeys (Macaca mulatta) were housed individually in standard nonhuman primate caging on a 12h light/12h dark cycle, room temperature (78 +/- 2 degrees F), and humidity at 60 +/- 20%. One pairing was maintained throughout the study; all other monkeys had extensive visual, auditory, and olfactory but limited tactile contact with monkeys housed in the same room. Monkeys received 2 meals per day at estimated ad libitum levels throughout the study. Water was always available ad libitum. Monkeys were monitored minimally 3 times daily by trained animal care staff. During baseline assessments, all monkeys were maintained on a commercially available closed formula monkey chow. After baseline assessment, four male rhesus monkeys remained on the healthy standard diet (SD), 10 male rhesus monkeys were begun on a high fat/high sucrose (HFS) diet and 10 male rhesus monkeys were begun on a high fat/high sucrose (HFS) diet plus Resveratrol, 80mg/day. After one year of dietary intervention, the amount of resveratrol was increased to 480mg/day for one additional year. Tissues were then harvested for the array experiments.

Project description:BackgroundInsulin resistance precedes metabolic syndrome which increases the risk of type 2 diabetes and cardiovascular disease. However, there is a lack of safe and long-lasting methods for the prevention and treatment of insulin resistance. Gut microbiota dysbiosis can lead to insulin resistance and associated glucose and lipid metabolic dysfunction. Thus, the role of gut microbiota in metabolic diseases has garnered growing interest. Curcumin, the active ingredient of tropical plant Curcuma longa, has excellent prospects for the prevention and treatment of metabolic diseases. However, due to the extremely low bioavailability of curcumin, the mechanisms by which curcumin increases insulin sensitivity remains to be elucidated. This study aimed to elucidate the role of gut microbiota in mediating the effects of curcumin on improving insulin sensitivity in high-fat diet (HFD)-fed mice.MethodsGlucose, insulin, and pyruvate tolerance were tested and hepatic triglycerides (TGs) content was measured in HFD-fed mice treated with curcumin (100 mg kg-1 d-1, p.o.) or vehicle for 4 weeks and aforementioned mice after gut microbiota depletion via antibiotic treatment for 4 weeks. Fecal microbiota transplantation (FMT) was conducted in endogenous gut microbiota-depleted HFD-fed mice. Glucose and lipid metabolic phenotypes were also measured in recipient mice colonized microbiota from vehicle- or curcumin-treated HFD-fed mice. The mechanisms underlying the effects of curcumin on increasing insulin sensitivity were testified by Western blotting, real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA).ResultsCurcumin ameliorated HFD-induced glucose intolerance, insulin resistance, pyruvate intolerance, and hepatic TGs accumulation, while these effects were mediated by gut microbiota. Curcumin induced insulin-stimulated Akt phosphorylation levels in insulin-regulated peripheral tissues. The inhibitory effects of curcumin on the expressions of genes involved in hepatic gluconeogenesis and de novo lipogenesis were dependent on gut microbiota. Meanwhile, curcumin upregulated the expression of fibroblast growth factor 15 (FGF15) through gut microbiota.ConclusionsThe effects of curcumin on promoting insulin sensitivity were dependent on gut microbiota in HFD-fed mice. Moreover, curcumin at least partly exerted its effects on increasing insulin sensitivity via FGF15 upregulation. This study provided new ideas on nutritional manipulations of gut microbiota for the treatment of metabolic diseases.

Project description:Diet-induced obesity is reported to induce a phenotypic switch in adipose tissue macrophages from an antiinflammatory M2 state to a proinflammatory M1 state. Telmisartan, an angiotensin II type 1 receptor antagonist and a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, reportedly has beneficial effects on insulin sensitivity. We studied the effects of telmisartan on the adipose tissue macrophage phenotype in high fat-fed mice. Telmisartan was administered for 5 weeks to high fat-fed C57BL/6 mice. Insulin sensitivity, macrophage infiltration, and the gene expressions of M1 and M2 markers in epididymal fat tissues were examined. Insulin- or a glucose-tolerance test showed that telmisartan treatment improved insulin resistance, decreasing the body weight gain, visceral fat weight and adipocyte size without affecting the amount of food intake. Telmisartan treatment reduced the number of CD11c-positive cells and crown-like structures. Telmisartan reduced the mRNA expressions of M1 macrophage markers, such as TNF-alpha and IL-6, and increased the expression of M2 markers, such as IL-10 and Mgl2. The reduction of M1 macrophage markers, as well as the increased gene expression of M2 markers especially IL-10, is a possible mechanism for the improvement of insulin sensitivity by telmisartan. Six-week-old male C57BL/6J mice were purchased from CLEA Japan. The mice were fed a chow that contained 10% of its calories from fat (control) or a high-fat diet (HFD) that contained 30% of its calories from fat for 24 weeks. The high fat-fed mice were randomized to 3 groups. Either telmisartan (~3 mg/kg/day) in drinking water (HFD+Tel), candesartan (~3 mg/kg/day) in drinking water (HFD+Can), or a HFD without any drugs (HFD) was administered for the next 5 weeks. Two mice were treated per group. Epididymal adipose tissues were rapidly removed from each mouse. Gene expression in epididymal fat tissue was analyzed using a GeneChip® system with the Mouse Genome 430 2.0 Array, which was spotted with 45,101 probe sets (Affymetrix, Santa Clara, CA, USA). Sample preparation for the array hybridization was performed according to the manufacturer’s instructions. In short, 5 μg of total RNA was used to synthesize double-stranded cDNA using the GeneChip® Expression 3′-Amplification Reagents One-Cycle cDNA Synthesis Kit (Affymetrix). Biotin-labeled cRNA was then synthesized from the cDNA using GeneChip® Expression 3′-Amplification Reagents for IVT Labeling (Affymetrix). After fragmentation, the biotinylated cRNA was hybridized to arrays at 45 °C for 16 h. The arrays were washed, stained with streptavidin-phycoerythrin, and scanned using a probe array scanner. The scanned chip was analyzed using the GeneChip Analysis Suite software (Affymetrix). Hybridization intensity data were converted into a presence/absence call for each gene, and changes in gene expression between experiments were detected by a comparison analysis. Data was shown as the fold change relative to the expression level of normal chow-fed mice.

Dataset Information

Resveratrol reduces the inflammatory response in adipose tissue and improves adipose insulin signaling in high-fat diet-fed mice.

Background

Methods

Results

Conclusion

Publications

Resveratrol reduces the inflammatory response in adipose tissue and improves adipose insulin signaling in high-fat diet-fed mice.

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