Curcumin improves adipocytes browning and mitochondrial function in 3T3-L1 cells and obese rodent model

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.

The pharmacological basis of the curcumin nutraceutical uses: an update

“…A study in mice showed that a very high-fat diet (VHFD) supplemented with curcumin (0.7% w/w) for 13 weeks led to a reduction in body weight gain and body fat, along with an increase in lean body mass (114). However, in disagreement with other studies (115), the same authors did not find any effect of curcumin on adipocyte cell size (114). On the other hand, other studies reported no effects of dietary curcumin on body weight and adiposity, in mice (116).…”

“…More recently, curcumin also enhanced the browning process as well as mitochondrial respiratory function in 3T3-L1 cells. These effects have been suggested to be related to stimulatory effects on PPAR, UCP-1, PR domain protein 16 (PRDM16), and PPAR coactivator-1 (PGC-1 expression levels (115).…”

Protective Effects of Curcumin in Cardiovascular Diseases—Impact on Oxidative Stress and Mitochondria

“…In addition, curcumin can induce the beiging of white adipocytes, which was shown in 3T3-L1 cells, but more importantly, in the primary white adipocytes from rats [127] (Figure 2). Moreover, in some of the in vivo models, upregulation of UCP1 as a sign of beiging was observed with or without a cold stimulus [124,128] (Figure 2). Interestingly, studies in lean animals or cells derived from them showed divergent effects of curcumin on beiging in different WAT depots.…”

Non-shivering Thermogenesis Signalling Regulation and Potential Therapeutic Applications of Brown Adipose Tissue

“…The AMPK signalling pathway is also involved in the BAT activation stimulated by many natural product ingredients, such as resveratrol, curcumin 134 , EGCG 167 and berberine 154 . Resveratrol is a phenylpropanoid present in various foods including red cabbage, spinach, berries, red wine, and peanuts.…”

“…Further research is needed to understand the anti-obesity mechanism of natural products in terms of thermogenesis. A growing number of natural products, such as curcumin 134 , thymol 145 , magnolol 144 and albiflorin 146 , have been shown to improve obesity by affecting the thermogenesis of brown adipose tissue through a variety of signalling pathways, and we will not go into detail here. With the development of methods and technologies, the mysteries of thermogenic pathways and their integration and control have begun to become apparent.…”