To investigate the functional effects of probiotic treatment on the gut microbiota, as well as liver and adipose gene expression in diet-induced obese mice. Male C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks to induce obesity, and then randomized to receive HFD+probiotic (Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, n = 9) or HFD+placebo (n = 9) for another 10 weeks. Normal diet (ND) fed mice (n = 9) served as non-obese controls. Diet-induced obese mice treated with probiotics showed reduced body weight gain and fat accumulation as well as lowered plasma insulin, leptin, total-cholesterol and liver toxicity biomarkers. A total of 151,061 pyrosequencing reads for fecal microbiota were analyzed with a mean of 6,564, 5,274 and 4,464 reads for the ND, HFD+placebo and HFD+probiotic groups, respectively. Gut microbiota species were shared among the experimental groups despite the different diets and treatments. The diversity of the gut microbiota and its composition were significantly altered in the diet-induced obese mice and after probiotic treatment. We observed concurrent transcriptional changes in adipose tissue and the liver. In adipose tissue, pro-inflammatory genes (TNFα, IL6, IL1β and MCP1) were down-regulated in mice receiving probiotic treatment. In the liver, fatty acid oxidation-related genes (PGC1α, CPT1, CPT2 and ACOX1) were up-regulated in mice receiving probiotic treatment. The gut microbiota of diet-induced obese mice appears to be modulated in mice receiving probiotic treatment. Probiotic treatment might reduce diet-induced obesity and modulate genes associated with metabolism and inflammation in the liver and adipose tissue.

Obesity‐induced inflammation contributes to the development of obesity‐related metabolic disorders such as insulin resistance, type 2 diabetes, fatty liver disease, and cardiovascular disease. In this study, we investigated whether dietary capsaicin can reduce obesity‐induced inflammation and metabolic disorders such as insulin resistance and hepatic steatosis. Male C57BL/6 obese mice fed a high‐fat diet for 10 weeks received a supplement of 0.015% capsaicin for a further 10 weeks and were compared with unsupplemented controls. Glucose intolerance was estimated by glucose tolerance tests. Transcripts of adipocytokine genes and the corresponding proteins were measured by reverse transcription‐PCR and enzyme‐linked immunosorbent assay, and macrophage numbers were determined by flow cytometric analysis. Transient receptor potential vanilloid type‐1 (TRPV‐1), peroxisome proliferator–activated receptor (PPAR)‐α, and PPARγ coactivator‐1α (PGC‐1α) mRNAs were also measured by RT‐PCR, and PPARα luciferase assays were performed. Dietary capsaicin lowered fasting glucose, insulin, leptin levels, and markedly reduced the impairment of glucose tolerance in obese mice. Levels of tumor necrosis factor‐α (TNFα), monocyte chemoattractant protein‐1 (MCP‐1), and interleukin (IL)‐6 mRNAs and proteins in adipose tissue and liver decreased markedly, as did macrophage infiltration, hepatic triglycerides, and TRPV‐1 expression in adipose tissue. At the same time, the mRNA/protein of adiponectin in the adipose tissue and PPARα/PGC‐1α mRNA in the liver increased. Moreover, luciferase assays revealed that capsaicin is capable of binding PPARα. Our data suggest that dietary capsaicin may reduce obesity‐induced glucose intolerance by not only suppressing inflammatory responses but also enhancing fatty acid oxidation in adipose tissue and/or liver, both of which are important peripheral tissues affecting insulin resistance. The effects of capsaicin in adipose tissue and liver are related to its dual action on PPARα and TRPV‐1 expression/activation.

Skeletal muscle inflammation and atrophy are closely associated with metabolic impairment such as insulin resistance. Quercetin, a natural polyphenol flavonoid, is known to elicit anti-inflammatory and antioxidant activities. In this study, we investigated its effect on obesity-induced skeletal muscle inflammation and atrophy in mice. Male C57BL/6 mice were fed a regular diet, a high-fat diet (HFD), and an HFD supplemented with quercetin for nine weeks. Quercetin reduced levels of inflammatory cytokines and macrophage accumulation in the skeletal muscle of the HFD-fed obese mice. It also reduced transcript and protein levels of the specific atrophic factors, Atrogin-1 and MuRF1, in the skeletal muscle of the HFD-fed obese mice, and protected against the reduction of muscle mass and muscle fiber size. In vitro, quercetin markedly diminished transcript levels of inflammatory receptors and activation of their signaling molecules (ERK, p38 MAPK, and NF-κB) in cocultured myotubes/macrophages, and this was accompanied by reduced expression of the atrophic factors. Together, these findings suggest that quercetin reduces obesity-induced skeletal muscle atrophy by inhibiting inflammatory receptors and their signaling pathway. Quercetin may be useful for preventing obesity-induced muscle inflammation and sarcopenia.

Objective: To determine whether chemokines, which play a pivotal role in monocyte/macrophage trafficking, modulate macrophage infiltration into and activation in the adipose tissues.Research Methods and Procedures: Various types of adipose tissue were isolated from different fat depots (e.g., mesenteric, epididymal, renal, and subcutaneous adipose tissues) from obese mice fed a high‐fat diet and from non‐obese controls fed a standard diet. The isolated tissues were cultured for 24, 48, and 72 hours. The level of monocyte chemoattractant protein‐1 (MCP‐1) expression and the amount of protein released were measured by reverse transcriptase‐polymerase chain reaction or enzyme‐linked immunosorbent assay, respectively. Chemotaxis assay was performed to measure the degree of macrophage migration. Macrophage activation was estimated by measuring the concentrations of nitric oxide and tumor necrosis factor α.Results: The level of MCP‐1 mRNA expression, protein content, and the amount of protein released significantly increased in the adipose tissues from the obese mice compared with those from the non‐obese mice. The mesenteric adipose tissue produced the highest levels of MCP‐1 protein among the four different fat depots. Mesenteric adipose tissue‐conditioned medium induced the highest degree of macrophage migration and strongly induced macrophages to produce proinflammatory mediators such as nitric oxide and tumor necrosis factor α. The neutralization of MCP‐1 in the adipose tissue‐conditioned medium significantly inhibited the migration and activation of macrophages.Discussion: Our findings suggest that MCP‐1 plays a crucial role in adipose tissue inflammatory response by activating and inducing the infiltration of macrophages into adipose tissues. MCP‐1 may be closely associated with visceral obesity‐related complications and, thus, may be a useful therapeutic target for modulating visceral obesity‐related diseases.