Abstract
Accumulating evidence suggests that mitochondrial dysfunction and adipocyte differentiation promote lipid accumulation in the development of obesity and diabetes. Curcumin is an active ingredient extracted from Curcuma longa that has been shown to exhibit antioxidant and anti-inflammatory potency in metabolic disorders. However, the underlying mechanisms of curcumin in adipocytes remain largely unexplored. We studied the effects of curcumin on adipogenic differentiation and mitochondrial oxygen consumption and analysed the possible mechanisms. 3T3-L1 preadipocytes were used to assess the effect of curcumin on differentiation of adipocytes. The Mito Stress Test measured by Seahorse XF Analyzer was applied to investigate the effect of curcumin on mitochondrial oxygen consumption in 3T3-L1 adipocytes. The effect of curcumin on the morphology of both white and brown adipose tissue (WAT and BAT) was evaluated in a high-fat diet-induced obese mice model. We found that curcumin dose-dependently (10, 20 and 35 µM) induced adipogenic differentiation and the intracellular fat droplet accumulation. Additionally, 10 µM curcumin remarkably enhanced mature adipocyte mitochondrial respiratory function, specifically, accelerating basic mitochondrial respiration, ATP production and uncoupling capacity via the regulation of peroxisome proliferator-activated receptor γ (PPARγ) (p < 0.01). Curcumin administration also attenuated the morphological changes in adipose tissues in high-fat diet-induced obese mice. Moreover, curcumin markedly increased the mRNA and protein expressions of mitochondrial uncoupling protein 1 (UCP1), PPARγ, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and PR domain protein 16 (PRDM16) in vivo and in vitro. Collectively, the results demonstrate that curcumin promotes the adipogenic differentiation of preadipocytes and mitochondrial oxygen consumption in 3T3-L1 mature adipocytes by regulating UCP1, PRDM16, PPARγ and PGC-1α expression.
Highlights
In recent decades, the obese population has skyrocketed worldwide, and insulin resistance due to increased adipose tissue mass, predominantly in viscera, has been recognized as a pivotal factor underlying the equivalent increase in type 2 diabetes mellitus
Curcumin could increase the triglyceride level in differentiated 3T3-L1 cells. These results suggest that curcumin could influence lipid profiles though promotion of adipocyte differentiation
GW9662 treatment attenuated the curcumin-induced upregulation of peroxisome proliferator-activated receptor γ 2 (PPARγ) activity to a level near that achieved with GW9662 alone. These results indicate that curcumin could partly enhance PPARγ RNA and protein expressions, and exert further pharmacological functions
Summary
The obese population has skyrocketed worldwide, and insulin resistance due to increased adipose tissue mass, predominantly in viscera, has been recognized as a pivotal factor underlying the equivalent increase in type 2 diabetes mellitus. Countermeasures to control the enlargement of white adipose tissue (WAT) and induction of white adipocyte browning may offer a new solution in fighting obesity and its associated diseases [1,2]. Methods to prevent the enlargement of adipose tissues (i.e. preventing fat accumulation) and induce the browning of white adipocytes (promoting energy expenditure) are the focus of current research on obesity and related diseases. Compounds that improve mitochondrial oxygen consumption may exhibit therapeutic efficacy in the prevention and control of many diseases due to energy metabolism disorders, such as obesity and diabetes
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