leptin and garcinol

Chronic inflammation is characterized by the upregulation of proinflammatory cytokines in obese adipose tissue. Accumulations of adipose tissue macrophages enhance a chronic inflammatory state in adipose tissues. Many studies have indicated that the adipocyte-related inflammatory response in obesity is characterized by an enhanced infiltration of macrophages. The aim of this work was to study the inhibitory effects of garcinol and pterostilbene on the change in inflammatory response due to the interaction between 3T3-L1 adipocytes and RAW 264.7 macrophages. In the TNF-α-induced 3T3-L1 adipocyte model, garcinol and pterostilbene significantly decreased the mRNA expression of COX-2, iNOS, IL-6, and IL-1β and IL-6 secretion by suppressing phosphorylation of p-IκBα and p-p65. In a coculture model of 3T3-L1 adipocytes and RAW 264.7 macrophages, pterostilbene suppressed IL-6 and TNF-α secretion and proinflammatory mRNA expression and also reduced the migration of macrophages toward adipocytes. In the RAW 264.7 macrophage-derived conditioned medium (RAW-CM)-induced 3T3-L1 adipocyte and 3T3-CM-induced RAW 264.7 macrophage models, pterostilbene significantly decreased IL-6 and TNF-α secretion and proinflammatory mRNA expression (COX-2, iNOS, IL-6, TNF-α, PAI-1, CRP, MCP-1, resistin, and leptin). Our findings suggest that garcinol and pterostilbene may provide novel and useful applications to reduce the chronic inflammatory properties of adipocytes. We also found that pterostilbene inhibits proinflammatory responses during the interaction between 3T3-L1 adipocytes and RAW 264.7 macrophages.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Cell Line, Tumor; Chemokine CCL2; Coculture Techniques; Cyclooxygenase 2; I-kappa B Proteins; Intercellular Signaling Peptides and Proteins; Interleukin-1beta; Interleukin-6; Leptin; Macrophages; Mice; NF-KappaB Inhibitor alpha; Nitric Oxide Synthase Type II; Phosphorylation; RNA, Messenger; Serpin E2; Stilbenes; Terpenes; Tumor Necrosis Factor-alpha

The aim of this work was to study the effects of garcinol and pterostilbene on cell proliferation and adipogenesis in 3T3-L1 cells. The results showed that garcinol and pterostilbene decreased the cell population growth and caused cell cycle arrest at the G2/M phase in 3T3-L1 preadipocytes. During adipocyte differentiation, both garcinol and pterostilbene had inhibitory effects on fat droplet formation and triacylglycerol accumulation. The data indicated that garcinol and pterostilbene could inhibit the glycerol-3-phosphate dehydrogenase (GPDH) activity by 97.8 and 61.5%, respectively, as compared to the control. Both garcinol and pterostilbene significantly attenuated the protein expressions of PPARγ and C/EBPα during 3T3-L1 adipocyte differentiation. Moreover, garcinol and pterostilbene caused an inhibition of lipid accumulation in the 3T3-L1 adipocyte differentiation phase. Garcinol and pterostilbene also significantly up-regulated the gene expression of adiponectin as well as down-regulated the gene expressions of leptin, resistin, and fatty acid synthase (FAS) in 3T3-L1 adipocyte differentiation. In 3T3-L1 adipocytes, garcinol significantly down-regulated the protein expressions of PPARγ and FAS as well as up-regulated the protein expressions of adipose triglyceride lipase (ATGL) and adiponectin. Garcinol also significantly up-regulated the gene expression of adiponectin as well as down-regulated the gene expressions of leptin and FAS. These results suggest that garcinol and pterostilbene have anti-adipogenic effects on preadipocytes and adipocytes.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Adiponectin; Animals; Cell Proliferation; Down-Regulation; Gene Expression; Leptin; Mice; Stilbenes; Terpenes