Obese adipose tissue is characterized by increased infiltration of macrophages, suggesting that they might represent an important source of inflammation. We have provided
in vitro evidence that ...saturated fatty acids, which are released from hypertrophied adipocytes via the macrophage-induced adipocyte lipolysis, serve as a naturally occurring ligand for Toll-like receptor 4 (TLR4) to induce the inflammatory changes in macrophages. Here we show the attenuation of adipose tissue inflammation in C3H/HeJ mice carrying a functional mutation in the TLR4 gene relative to control C3H/HeN mice during a 16-week high-fat diet. We also find that adiponectin mRNA expression is significantly reduced by co-culture of hypertrophied 3T3-L1 adipocytes and C3H/HeN peritoneal macrophages, which is reversed, when co-cultured with C3H/HeJ peritoneal macrophages. This study provides
in vivo evidence that TLR4 plays a role in obesity-related adipose tissue inflammation and thus helps to identify the therapeutic targets that may reduce obesity-induced inflammation and the metabolic syndrome.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Vitamin D is known to be effective for the prevention of muscle atrophy, such as age-related sarcopenia. However, vitamin D action in skeletal muscle tissue and muscle cells is largely unknown. We ...previously found that a transcription factor, FOXO1 gene expression, was induced in various muscle atrophy conditions causing muscle atrophy by upregulating atrophy-related genes, including atrogin 1 (ubiquitin ligase) and cathepsin L (lysosomal proteinase). In this study, we found that vitamin D inhibited FOXO1-mediated transcriptional activity in a reporter gene assay. Moreover, vitamin D suppressed the glucocorticoid-induced gene expression of atrogin 1 and cathepsin L in C2C12 myoblasts. Thus, vitamin D may prevent muscle atrophy via the FOXO1-mediated pathway in muscle cells.
Postmenopausal women as well as rodents after ovariectomy. which results in a lack of estrogen, can become obese. Ovariectomy-induced obesity in mice is associated with a decrease in oxygen ...consumption, indicating repressed energy expenditure. In this study, to elucidate the mechanism of weight gain after ovariectomy, we examined the expression patterns of genes related to energy expenditure and lipid metabolism, in mouse tissues including adipose tissue and skeletal muscle. In adipose tissue and skeletal muscle, at 2-4 wk after ovariectomy, levels of nuclear receptors and cofactors involved in energy expenditure such as ERR1. PPARalpha and PPARdelta, and PGC1alpha and PGC1beta were lower than in control mice. mRNA levels of their targets, medium-chain acyl coenzyme A dehydrogenase and acetyl CoA oxidase, enzymes for fatty acid beta-oxidation, were lower, In addition, the expression of PPARgamma and SREBP1, transcription factors important for lipogenesis, was decreased, as well as that of acetyl CoA carboxylase and fatty acid synthase, enzymes for fatty acid synthesis, and diacyl glycerol acetyl transferase 1 and 2, enzymes for triglyceride synthesis. These changes in gene expression are consistent with the obese phenotype in mice after ovariectomy. Thus a decrease in the expression of energy expenditure-related genes in adipose tissue and skeletal muscle could, in part, be responsible for obesity after ovariectomy.
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