Berberine is an isoquinoline alkaloid found in Rhizoma coptidis, and elicits anti-inflammatory effects through diverse mechanisms. Based on previous reports that activating transcription factor-3 (ATF-3) acts as a negative regulator of LPS signaling, the authors investigated the possible involvement of ATF-3 in the anti-inflammatory effects of berberine. It was found berberine concentration-dependently induced the expressions of ATF-3 at the mRNA and protein levels and concomitantly suppressed the LPS-induced productions of proinflammatory cytokines (TNF-α, IL-6, and IL-1β). In addition, ATF-3 knockdown abolished the inhibitory effects of berberine on LPS-induced proinflammatory cytokine production, and prevented the berberine-induced suppression of MAPK phosphorylation, but had little effect on AMPK phosphorylation. On the other hand, the effects of berberine, that is, ATF-3 induction, proinflammatory cytokine inhibition, and MAPK inactivation, were prevented by AMPK knockdown, suggesting ATF-3 induction occurs downstream of AMPK activation. The in vivo administration of berberine to mice with LPS-induced endotoxemia increased ATF-3 expression and AMPK phosphorylation in spleen and lung tissues, and concomitantly reduced the plasma and tissue levels of proinflammatory cytokines. These results suggest berberine has an anti-inflammatory effect on macrophages and that this effect is attributable, at least in part, to pathways involving AMPK activation and ATF-3 induction.
Activating Transcription Factor 3* ; AMP-Activated Protein Kinases ; Animals ; Berberine* ; Cytokines ; Endotoxemia ; Hand ; Inflammation ; Interleukin-6 ; Lung ; Macrophages* ; Mice ; Phosphorylation ; Plasma ; RNA, Messenger ; Spleen

B cell activation factor (BAFF) is a novel member of the TNF ligand superfamily, mainly produced by myeloid cells. BAFF has been shown to participate in B-cell survival and B- and T-cell maturation. BAFF expression in adipocytes has been recently demonstrated. In the current study, we verified that BAFF expression is increased during adipocyte differentiation. BAFF expression was augmented by TNF-alpha treatment and was decreased by rosiglitazone treatment. BAFF secretion in lean and in ob/ob mice sera were compared and smaller amount of BAFF was secreted in ob/ob mice. mRNA and protein expression were different between epididymal and visceral adipose tissue. BAFF expression was also increased in ob/ob mouse adipose tissue. We sought to identify known BAFF receptors (BAFF-R, BCMA, and TACI) in adipocytes, and determined that all three were present and upregulated during adipocyte differentiation. However, the expression of TACI was distinct from that of BAFF-R and BCMA under TNF-alpha and BAFF ligand treatment. BAFF-R and BCMA expression levels were upregulated under pro-inflammatory conditions, but TACI was reduced. Conversely, BAFF-R and BCMA expression levels were downregulated by rosiglitazone treatment, but TACI was increased. Taken together, our results suggest that BAFF may be a new adipokine, representing a link between obesity and inflammation.
Adipocytes/cytology ; Adipokines/biosynthesis/*physiology ; Animals ; B-Cell Activating Factor/biosynthesis/*physiology ; B-Cell Activation Factor Receptor/metabolism ; Cell Differentiation ; Hypoglycemic Agents/pharmacology ; Inflammation/*metabolism ; Mice ; Obesity/*metabolism ; Thiazolidinediones/pharmacology ; Tumor Necrosis Factor-alpha/pharmacology

BACKGROUND: Food restriction has been reported to ameliorate diabetes and obesity. In this study, we examined the effects of the food restriction on phenotypes of TALLYHO/JngJ (TH) mouse, a recently developed diabetic model animal. METHODS: 3 week-old TH mice were divided into 2 groups (n = 20 each for food-restricted (THR) and free-fed (THF)) and THR mice were fed the same amount of food as normal control mice (C57BL/6, n = 20). Body weight was weekly monitored till 14 weeks of age. The half of animals were sacrificed at 8 weeks of age, and liver, kidney, and fat weight were measured. The histopathology of liver and brown fat tissues and mRNA expression of leptin in adipose tissue were analyzed. The oral glucose tolerance test and insulin resistance test was done at 14 weeks of age. The plasma concentrations of glucose, free fatty acid, triglyceride, cholesterol and leptin were analyzed. RESULTS: The THR mice had lower body weights than the THF mice, similar to C57BL/6 mice, with reduced fat deposition in liver and brown fat tissue. The plasma levels of glucose, triglyceride and free fatty acid were decreased in the THR group. The THR mice, however, carried more fat than normal mice, with increased plasma leptin concentration and leptin mRNA expression in fats and no alteration in plasma cholesterol levels. Furthermore, the THR mice revealed glucose intolerance with impaired after-meal insulin secretion and slight insulin resistance CONCLUSION: The food restriction apparently ameliorated the obesity and diabetic phenotypes of TH mice. However, plasma concentration of cholesterol were not improved in THR mice with increased adiposity index and glucose intolerance, suggesting the genetically prone tendency of obesity and diabetes development in TH mice possibly with an impairment in cholesterol metabolism.
Adipose Tissue ; Adipose Tissue, Brown ; Adiposity ; Animals ; Body Weight ; Cholesterol ; Diabetes Mellitus ; Fats ; Glucose ; Glucose Intolerance ; Glucose Tolerance Test ; Insulin ; Insulin Resistance ; Kidney ; Leptin ; Liver ; Mice ; Obesity ; Phenotype ; Plasma ; RNA, Messenger