Abstract
Limonoids are phytochemicals with a variety of biological properties. In the present study, we elucidated the molecular mechanism of suppression of adipogenesis in adipocytes by a limonoid, 7-deacetoxy-7-oxogedunin (CG-1) from Carapa guianensis (Meliaceae), known as andiroba. CG-1 reduced the accumulation of intracellular triglycerides in a concentration-dependent manner. The expression levels of the adipogenic, lipogenic, and lipolytic genes were decreased by CG-1 treatment, whereas the glycerol release level was not affected. When CG-1 was added into the medium during days 0-2 of 6-days-adipogenesis, the accumulation of intracellular lipids and the mRNA levels of the adipogenesis-related genes were decreased. In addition, the phosphorylation level of insulin receptor substrate-1 (IRS-1) and Akt in the early phase of adipocyte differentiation (within 1 day after initiating adipocyte differentiation) was reduced by CG-1. Furthermore, insulin-activated translocation of glucose transporter 4 to the plasma membranes in adipocytes was suppressed by CG-1, followed by decreased glucose uptake into the cells. These results indicate that an andiroba limonoid CG-1 suppressed the accumulation of intracellular lipids in the early phase of adipocyte differentiation through repression of IRS-1/Akt-mediated glucose uptake in adipocytes.
Highlights
Obesity is a public health problem both in developed and developing countries [1]
We investigated of the investigated the effects of CG-1 on the insulin receptor substrate-1 (IRS-1)/Akt signaling and the suppression of adipogenesis effects cells
We found that a purified from the seeds of andiroba, C. guianensis, Meliaceae showed anti-adipogenic effects in mouse limonoid CG-1 purified from the seeds of andiroba, C. guianensis, Meliaceae showed anti-adipogenic adipocyte 3T3-L1 cells
Summary
Obesity is a public health problem both in developed and developing countries [1]. Obesity is defined as an abnormal increase in adipose tissue mass, and is associated with the occurrence of lifestyle-related diseases such as hyperlipidemia, diabetes mellitus, hypertension, and cardiovascular disease [1,2,3]. Adipocytes are specialized cells that store lipids as an energy source to regulate lipid metabolism and energy balance in the body. An excess amount of lipid accumulation in adipose cells results in obesity. Elucidation of the regulation mechanism of adipocyte differentiation is critical to control adipogenesis and obesity and to develop anti-obesity medicines. Adipocyte differentiation is influenced by various factors such as hormones, growth factors, gene expression, and environmental conditions. Adipocyte differentiation (adipogenesis) proceeds via a multi-step process, which includes a cascade of various transcription factors and cell-cycle proteins [4]
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