Wang, Xiong, Zhang, Yanhua, Zhang, Lei, Wang, Wenli, Che, Huilian, and Zhang, Yali
Substantial evidence suggests that pepper consumption is associated with a reduced risk of obesity-related complications. However, whether piperine, the main component of pepper, improves obesity-induced hepatic lipid accumulation and insulin resistance and the action mechanism of piperine still remain unclear. We hypothesized that piperine attenuates high-fat diet (HFD)-induced obesity and improves the related metabolic complications in HFD-induced obese rats. Adult Sprague-Dawley (SD) male rats were fed a control diet (CON) or an HFD for 16 weeks. Obese rats were divided into 4 groups: HFD and HFD with daily gavage of piperine 2.7 mg/kg body weight (PIP-Low), 13.5 mg/kg body weight (PIP-Medium), and 27 mg/kg body weight (PIP-High) for another 8 weeks. Rats were euthanized after an 8-hour fast, and the liver, heart, kidney, and white adipose tissue were collected and stored at –80 °C. Piperine administration significantly reduced weight gain, plasma insulin, and glucose concentration. For oral piperine at a dose of 27 mg/kg body weight, body weight significantly decreased by 5.7% compared with that in the HFD group. Additionally, oral piperine administration considerably reduced serum triglyceride concentration. Furthermore, piperine administration reversed the HFD-induced downregulation of adenosine 5′-monophosphate-activated protein kinase (AMPK) signaling molecules and increased the plasma levels of adiponectin and the messenger RNA expression of the adiponectin receptor; additionally, it increased the phosphorylation of phosphatidylinositol-3 kinase (PI3K) and protein kinase B. Overall, oral piperine administration reversed HFD-induced liver lipid accumulation and insulin resistance, possibly via the inactivation of adiponectin-AMPK and PI3K-Akt signaling. These findings imply that piperine could serve as an effective agent for healthy weight loss. [Display omitted] Molecular mechanism of oral administration piperine improves high-fat diet (HFD)-induced metabolic syndrome in rats. Piperine upregulates the level of adiponectin in plasma, thereby activating the AMPK signaling pathway through LKB1. Further, it leads to downregulated fat synthesis-related genes (Fas, ACC), and promotes fat burning and consumption. In addition, piperine activates the PI3k-Akt signaling pathway to improve insulin resistance induced by an HFD. Abbreviations: ACC, acetyl-CoA carboxylase; AdipoR, adiponectin receptor; AKT, protein kinase B; AMPK, adenosine 5′-monophosphate-activated protein kinase; CPT-1, carnitine palmitoyl transferase; FAS, fatty acid syntheses; HFD, high-fat diet; IRS, insulin receptor substrate; LKB1, liver kinase B1; PI3K, phosphatidylinositol-3 kinase; PPAR-γ, peroxisome proliferators-activated receptor-γ; SREBP1, sterol regulatory element binding proteins. [ABSTRACT FROM AUTHOR]