Fluvastatin Sodium Ameliorates Obesity through Brown Fat Activation

Abstract

Brown adipose tissue (BAT), an organ that burns energy through uncoupling thermogenesis, is a promising therapeutic target for obesity. However, there are still no safe anti-obesity drugs that target BAT in the market. In the current study, we performed large scale screening of 636 compounds which were approved by Food and Drug Administration (FDA) to find drugs that could significantly increase uncoupling protein 1 (UCP1) mRNA expression by real-time PCR. Among those UCP1 activators, most of them were antibiotics or carcinogenic compounds. We paid particular attention to fluvastatin sodium (FS), because as an inhibitor of the cellular hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase, FS has already been approved for treatment of hypercholesteremia. We found that in the cellular levels, FS treatment significantly increased UCP1 expression and BAT activity in human brown adipocytes. Consistently, the expression of oxidative phosphorylation-related genes was significantly increased upon FS treatment without differences in adipogenic gene expression. Furthermore, FS treatment resisted to high-fat diet (HFD)-induced body weight gain by activating BAT in the mice model. In addition, administration of FS significantly increased energy expenditure, improved glucose homeostasis and ameliorated hepatic steatosis. Furthermore, we reveal that FS induced browning in subcutaneous white adipose tissue (sWAT) known to have a beneficial effect on energy metabolism. Taken together, our results clearly demonstrate that as an effective BAT activator, FS may have great potential for treatment of obesity and related metabolic disorders.

Allicin Regulates Energy Homeostasis through Brown Adipose Tissue

“…The regulation of energy homeostasis, including food intake, energy expenditure, and body adiposity, is crucial to a healthy body (Murphy and Bloom, 2006;Farooqi and O'Rahilly, 2005). Obesity is the result of an imbalance in energy homeostasis, which is caused by energy intake that exceeds energy expenditure, and excess energy is stored in fat in the form of triglycerides (TGs), leading to adiposity (Yuan et al, 2017) and causing a series of metabolic diseases, such as insulin resistance, type 2 diabetes mellitus, cardiovascular disease, cancer, inflammation, and other related diseases (Yin et al, 2019). At present, obesity has become one of the fastest-growing non-communicable diseases, and global estimates have shown that by 2030, 38% adults would be overweight and 20% will develop obesity (Nishtar et al, 2016;Geserick et al, 2018).…”

Jinlida Granules Reduce Obesity in db/db Mice by Activating Beige Adipocytes

“…AutoDock Vina 1.1.2 was used to conduct the docking task [ 24 ]. Through literature search, we obtained five small molecular compounds (berberine [ 25 ], thiazolidinedione [ 26 ], rhein [ 27 ], formononetin [ 28 ], and fluvastatin sodium [ 29 ]), which can activate UCP1 as the control. The compound structures were downloaded from the PubChem database in SDF format [ 30 ].…”

Impact of Adaptive Thermogenesis in Mice on the Treatment of Obesity

“…Overfeeding activates BAT's diet-induced thermogenesis [92]. Thus, several studies have focused on natural or chemical drugs to enhance thermogenesis such as ginger [110], tea seed oil [111], berberine [112], butein [113], capsaicin [114], flavonoids such as quercetin [115], calcium supplement [116] or fluvastatin sodium [117], among others.…”