The inducible co-activator PGC-1α plays a crucial role in adaptive thermogenesis and increases energy expenditure in brown adipose tissue (BAT). Meanwhile, chronic inflammation caused by infiltrated-macrophage in the white adipose tissue (WAT) is a target for the treatment of obesity. Bofutsushosan (BF), a traditional Chinese medicine composed of 17 crude drugs, has been widely used to treat obesity in China, Japan, and other Asia countries. However, the mechanism underlying anti-obesity remains to be elucidated. In the present study, we demonstrated that BF oral administration reduced the body weight of obese mice induced by high-fat diet (HFD) and alleviated the level of biochemical markers (P < 0.05), including blood glucose (Glu), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C) and insulin. Our further results also indicated that oral BF administration increased the expression of PGC-1α and UCP1 in BAT. Moreover, BF also reduced the expression of inflammatory cytokines in WAT, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). These findings suggested that the mechanism of BF against obesity was at least partially through increasing gene expression of PGC-1α and UCP1 for energy consumption in BAT and inhibiting inflammation in WAT.
Adipose Tissue, Brown ; drug effects ; immunology ; Adipose Tissue, White ; drug effects ; immunology ; Animals ; Cytokines ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Energy Metabolism ; drug effects ; Female ; Humans ; Interleukin-6 ; genetics ; immunology ; Mice ; Obesity ; drug therapy ; genetics ; immunology ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; genetics ; immunology ; Tumor Necrosis Factor-alpha ; genetics ; immunology ; Uncoupling Protein 1 ; genetics ; metabolism

The incidence of diabetes mellitus is increasing among companion animals. This disease has similar characteristics in both humans and animals. Diabetes is frequently identified as an independent risk factor for infections associated with increased mortality. In the present study, homozygous diabetic (db/db) mice were infected with Listeria (L.) monocytogenes and then treated with the anti-diabetic drug exendin-4, a glucagon-like peptide 1 analogue. In aged db/db mice, decreased CD11b+ macrophage populations with higher lipid content and lower phagocytic activity were observed. Exendin-4 lowered high lipid levels and enhanced phagocytosis in macrophages from db/db mice infected with L. monocytogenes. Exendin-4 also ameliorated obesity and hyperglycemia, and improved ex vivo bacteria clearance by macrophages in the animals. Liver histology examined during L. monocytogenes infection indicated that abscess formation was much milder in exendin-4-treated db/db mice than in the control animals. Moreover, mechanistic studies demonstrated that expression of ATP binding cassette transporter 1, a sterol transporter, was higher in macrophages isolated from the exendin-4-treated db/db mice. Overall, our results suggest that exendin-4 decreases the risk of infection in diabetic animals by modifying the interaction between intracellular lipids and phagocytic macrophages.
ATP-Binding Cassette Transporters/metabolism ; Age Factors ; Animals ; Blood Chemical Analysis ; Cholesterol/metabolism ; Diabetes Mellitus, Type 2/*drug therapy/genetics ; Dyslipidemias/drug therapy/genetics ; Female ; Hyperglycemia/drug therapy/genetics ; Hypoglycemic Agents/*therapeutic use ; Injections, Intraperitoneal ; *Lipid Metabolism/drug effects ; Listeria monocytogenes/*drug effects/immunology ; Listeriosis/*drug therapy/immunology/microbiology ; Macrophages/drug effects/*metabolism ; Mice ; Obesity/drug therapy/genetics ; Peptides/*therapeutic use ; Phagocytosis/drug effects ; Venoms/*therapeutic use

Whether supplementation of curcuminoids decreases serum adipocyte-fatty acid binding protein (A-FABP) level and whether this decrease benefits glucose control is unclear. One-hundred participants (n=50 administered curcuminoids, n=50 administered placebo) from our previous report on the effect of curcuminoids on type 2 diabetes in a 3-month intervention were assessed for levels of serum A-FABP, oxidative stress, and inflammatory biomarkers. Curcuminoids supplementation led to significant decreases in serum A-FABP, C-reactive protein (CRP), tumor necrosis factor-α, and interleukin-6 levels. Curcuminoids supplementation also significantly increased serum superoxide dismutase (SOD) activity. The change in serum A-FABP levels showed positive correlations with changes in levels of glucose, free fatty acids (FFAs), and CRP in subjects supplemented with curcuminoids. Further stepwise regression analysis showed that A-FABP was an independent predictor for levels of FFAs, SOD, and CRP. These results suggest that curcuminoids may exert anti-diabetic effects, at least in part, by reductions in serum A-FABP level. A-FABP reduction is associated with improved metabolic parameters in human type 2 diabetes.
Biomarkers ; blood ; Blood Glucose ; analysis ; Curcumin ; administration & dosage ; pharmacology ; therapeutic use ; Diabetes Mellitus, Type 2 ; blood ; complications ; drug therapy ; immunology ; Fatty Acid-Binding Proteins ; blood ; Humans ; Hypoglycemic Agents ; administration & dosage ; pharmacology ; therapeutic use ; Obesity ; blood ; complications ; drug therapy ; immunology ; Oxidative Stress ; drug effects ; immunology ; Treatment Outcome

PURPOSE: Low grade inflammation is a well-known characteristic in obese subjects. We investigated body weight changes and inflammatory markers after 12-week intervention trial. MATERIALS AND METHODS: Twenty-six obese subjects were enrolled and 19 (13 men and 6 women) completed the study. Sibutramine is an FDA-approved drug for body weight control; therefore, we chose this drug as the standard treatment medication in this study. Patients were randomly allocated to receive an anti-inflammatory agent (Diacerein treatment group; n = 12) or placebo (n = 7) for 12 weeks. Anthropometry, body proportion by dual-energy X-ray absorptiometry, and metabolic parameters at the beginning and end of study were measured and compared. RESULTS: The treatment group had a tendency towards more reduction in anthropometry as compared to the placebo group, in body weight reduction (- 7.0 kg vs. - 4.6 kg), body mass index (- 2.51 kg/m2 vs. - 1.59 kg/m2), and waist circumference (- 7.3 cm vs. - 4.4 cm). These reductions were not statistically significant. Changes in levels of high-sensitivity C-reactive protein and adiponectin in the treatment group were more favorable than in the placebo group. CONCLUSION: This small pilot study showed no statistical difference for changes in anthropometry, and inflammatory markers between the two groups. Therefore, we could not find any additional effects of Diacerein on weight loss and inflammatory variables in this study.
Absorptiometry, Photon ; Adiponectin/blood ; Adult ; Anthraquinones/*therapeutic use ; Anti-Inflammatory Agents/*therapeutic use ; Appetite Depressants/therapeutic use ; C-Reactive Protein/analysis ; Cyclobutanes/*therapeutic use ; Double-Blind Method ; Female ; Humans ; Inflammation ; Lipoproteins, LDL/blood ; Male ; Obesity/*drug therapy/immunology ; Pilot Projects ; Tumor Necrosis Factor-alpha/blood ; Waist Circumference/drug effects/immunology ; Weight Loss/drug effects/*immunology

OBJECTIVETo investigate the effect of berberine on serum levels of TNF-alpha, IL-6 and adiponectin in obese mice induced by high fat diet and its potential molecular mechanisms.

METHODNormal male Kunming mice were randomly divided into two groups taking normal chow (NC, n = 10) and high fat diet (HF, n = 30), respectively. After 13 weeks, HF mice were continuously given high fat diet and divided into three groups, model group (BM), low-dosage of berberine group (BL) and high-dosage of berberine group (BH). Mice in BL and BH were administered berberine by gavage at the dosage of 50 mg x kg(-1) and 150 mg x kg(-1), respectively. Two weeks later, oral glucose tolerance test was performed. At the end of the experiment, the mice were killed and blood samples were collected. The epididymal fat tissue and liver were removed promptly and weighed. The serum cytokine was measured by ELISA. The levels of IkappaB kinase beta (IKK-beta) and IKK-beta (ser181) were detected by Western blotting.

RESULTSerum levels of TNF-alpha, IL-6 in mice of BM were significantly higher than those in NC (P < 0.05). After two-week treatment of berberine, serum levels of TNF-alpha, IL-6 in BL and BH were lower than those in BM (P < 0.05, respectively). However, there were no significant difference of adiponectin among four groups. The degrees of phosphorylation of IKK-beta (ser181) were decreased in liver and adipose tissue in BH in comparison to that in BM, although the expression of total IKK-beta did not change. Furthermore, the glucose tolerance was improved, while the body weight and epididymal fat were reduced in mice treated with berebrine. 9: Berberine is able to reduce inflammatory cytokines expression and inhibit activation of IKK-beta (ser181) in obese mice, which may partly explain the therapeutic effect of berberine on insulin resistance and abnormal glucose metabolism.

Animals ; Berberine ; administration & dosage ; Dietary Fats ; administration & dosage ; adverse effects ; Disease Models, Animal ; Glucose Tolerance Test ; Humans ; Inflammation Mediators ; blood ; Interleukin-6 ; blood ; Liver ; drug effects ; immunology ; metabolism ; Male ; Mice ; Mice, Obese ; Obesity ; blood ; drug therapy ; immunology ; metabolism ; Signal Transduction ; drug effects ; Tumor Necrosis Factor-alpha ; blood