Curcumin improves glycolipid metabolism through regulating peroxisome proliferator activated receptor γ signalling pathway in high-fat diet-induced obese mice and 3T3-L1 adipocytes

Abstract

Curcumin is an active component derived from Curcuma longa L. which is a traditional Chinese medicine that is widely used for treating metabolic diseases through regulating different molecular pathways. Here, in this study, we aimed to comprehensively investigate the effects of curcumin on glycolipid metabolism in vivo and in vitro and then determine the underlying mechanism. Male C57BL/6 J obese mice and 3T3-L1 adipocytes were used for in vivo and in vitro study, respectively. Our results demonstrated that treatment with curcumin for eight weeks decreased body weight, fat mass and serum lipid profiles. Meanwhile, it lowered fasting blood glucose and increased the insulin sensitivity in high-fat diet-induced obese mice. In addition, curcumin stimulated lipolysis and improved glycolipid metabolism through upregulating the expressions of adipose triglyceride lipase and hormone-sensitive lipase, peroxisome proliferator activated receptor γ/α (PPARγ/α) and CCAAT/enhancer binding proteinα (C/EBPα) in adipose tissue of the mice. In differentiated 3T3-L1 cells, curcumin reduced glycerol release and increased glucose uptake via upregulating PPARγ and C/EBPα. We concluded that curcumin has the potential to improve glycolipid metabolism disorders caused by obesity through regulating PPARγ signalling pathway.

Metabolic benefits of curcumin supplementation in patients with metabolic syndrome: A systematic review and meta‐analysis of randomized controlled trials

“…Antidiabetic effect of curcumin supplement, at least in part, is due to decreasing in serum free fatty acids (Na et al, ). The possible mechanisms of the effect of curcumin on glycemia in human/animal diabetes models and in vitro may be understood as follows: (a) decrease tumor necrosis factor‐α (TNF‐α) levels (El‐Azab et al, ; El‐Moselhy et al, ), (b) decrease plasma free fatty acids (El‐Moselhy et al, ); through increasing peroxisomal fatty acid β‐oxidation) (Asai & Miyazawa, ); (c) attenuate oxidative stress (Murugan & Pari, ); (d) decrease circulating concentrations of resistin and fetuin‐A (Sahebkar, ); (e) inhibit nuclear factor‐kappa B (NF‐κB) activation (Soetikno et al, ), (f) inhibit protein carbonyl (Suryanarayana et al, ); (g) inhibits lipid peroxidation (El‐Azab, Attia, & El‐Mowafy, ), (h) inhibits lysosomal enzyme activities (Chougala et al, ); (i) induce the mRNA and protein expression of PPAR‐γ (Nishiyama et al, ; Pan et al, ); (j) active nuclear factor erythroid‐2‐related factor‐2 (Nrf2) function (He et al, ); (k) increase plasma insulin level lipoprotein lipase activity (Seo et al, ); (l) down‐regulation of JNK phosphorylation and activity (Shao‐Ling et al, ).…”

“…Moreover, the findings of a study confirmed the efficacy of curcumin supplementation in significantly reducing liver fat content, BMI, and serum levels of total cholesterol, LDL‐C, TG, glucose, and HbA1c of patients with nonalcoholic fatty liver disease and MetS (Rahmani et al, ). The multiple mechanisms of curcumin on lipids may be explained as follows: (a) decrease oxidative stress (Lin et al, ); (b) inhibit membrane translocation and GLUT2‐mediated gene expression; (c) increase expression of the advanced glycation end products receptor (Lin et al, ); (d) increase expression LDL‐receptor (enhance plasma removal and biliary excretion of cholesterol) (Sahebkar, ); (e) increase expression of genes involved in lipid accumulation (Hegarty et al, ); (f) stimulate the activity of PPAR‐γ (Hegarty et al, ); (g) activate the process of lipolysis of TGs (Pan et al, ; Vázquez‐Vela et al, ); (h) regulate adipocyte differentiation and macrophage activation (Gonzales & Orlando, ; Gustafson & Smith, ); (i) inhibit the foam cell formation (Li et al, ); (j) decrease intestinal absorption of cholesterol (Sahebkar, ); (k) downregulate several enzymes and receptors involved in lipogenesis (Sahebkar, ); (l) stimulate fatty acid oxidation, 13‐reduce glycerol lipid synthesis (Ejaz et al, ). However, it is unclear which mechanism will have the most important impact.…”

“…The expression of PPARγ and C/EBPα in mice and in adipocytes (3T3‐L1 cells) by curcumin improved insulin resistance, glucose uptake (Pan et al, ), lipolysis of circulating TGs, and their storage in adipose tissue (Kim et al, ; B. Lee et al, ). But a dose of curcumin is important for upregulating the protein expression of PPARγ and C/EBPα in adipocytes, and a high dose of curcumin was ineffective in the adipocyte (Pan et al, ).…”

Benefits of curcumin in brain disorders

“…PPAR‐γ influences the activity of several intracellular second messengers and their signaling cascade, including regulation of insulin sensitivity, glucose homeostasis, fatty acid oxidation, immune responses, redox balance, cardiovascular integrity, and cell fate . Recent studies have reported that activation of PPAR‐γ reduces the development and progression of neurodegenerative diseases by altering the expression of NF‐κB cascade . PPAR‐γ is highly expressed in hippocampal region of the brain .…”

“…[130][131][132] Recent studies have reported that activation of PPAR-γ reduces the development and progression of neurodegenerative diseases by altering the expression of NF-κB cascade. 131,133,134 PPAR-γ is highly expressed in hippocampal region of the brain. 135 PPAR-γ directly or indirectly influences the expression of genes (TFAM, NRF1, NRF2, Bax, and Bcl-2) that are involved in neurodegeneration.…”