Resveratrol Maintains Lipid Metabolism Homeostasis via One of the Mechanisms Associated with the Key Circadian Regulator Bmal1

Abstract

Resveratrol (RES) possesses anti-inflammatory and anti-oxidant activities, and it can prevent liver lipid metabolism disorders in obese and diabetic individuals. This study elucidated the mechanisms of brain and muscle Arnt-like protein-1 (Bmal1) in the protective effects of RES against liver lipid metabolism disorders. The results indicated that RES ameliorated free fatty acid (FFA)-induced (oleic acid (OA): palmitic acid (PA) = 2:1) glycolipid metabolic disorders in hepatocytes. Simultaneously, RES partially reverted the relatively shallow daily oscillations of FFA-induced circadian clock gene transcription and protein expression in HepG2 cells. RES also attenuated FFA-triggered reactive oxygen species (ROS) secretion and restored mitochondrial membrane potential consumption, as well as the restoration of mitochondrial respiratory complex expression. This study provides compelling evidence that RES controls intracellular lipid metabolic imbalance in a Bmal1-dependent manner. Overall, RES may serve as a promising natural nutraceutical for the regulation of lipid metabolic disorders relevant to the circadian clock.

Antioxidant and Hypolipidemic Activity of Açai Fruit Makes It a Valuable Functional Food

“…Many antioxidant molecules, such as plant phenolics (including simple flavonoids, coumarins, stilbenes, hydrolyzable and condensed tannins, lignans, and lignins) are known to show a peculiar hormesis effect on cells, namely at low doses they show protective effects on lipid metabolism, whereas, at higher doses they induce cell toxicity [ 28 ]. Few studies reported that resveratrol inhibits cell viability in a dose- and time-dependent manner [ 29 ]. For these reasons we tested açai extract at low doses on different cell models.…”

Is There a Utility of Chrono‐Specific Diets in Improving Cardiometabolic Health?

“…Furthermore, DHA from the algal oil was also shown to regulate the circadian rhythm of Phase shift in Clock and Bmal1. [110] blood lipids in mice via the action of rhythmic nuclear receptors and downstream pathways involved in cholesterol and bile acid synthesis, thereby improving blood lipid profiles. [71] Similarly for MUFAs, oleic acid was capable of restoring the rhythmicity of clock genes in stomach and jejunal explants obtained from individuals with morbid obesity.…”

“…Compounds such as Resveratrol, nobiletin, piceatannol, and ursolic acid have been shown to be capable of ameliorating high fat diet‐induced circadian desynchrony in hepatocyte cultures and animal studies, by reverting disruptions and phase‐shifting clock genes involved in lipid and glucose metabolism. [ 109–112 ] Similarly, capsaicin was also shown to alleviate impaired glucose uptake, circadian misalignment, and redox imbalance induced by insulin resistance in HepG2 cells. [ 113 ] The intake of melanoidins were also capable of restoring circadian rhythmicity of gut microflora profiles in mice (from a high fat diet‐induced dysbiosis), thereby increasing the abundance of SCFA producers and reducing the oscillations of inflammatory species.…”

Piperine Improves Lipid Dysregulation by Modulating Circadian Genes Bmal1 and Clock in HepG2 Cells

“…Multiple studies have shown that the misalignment of circadian rhythms is associated with various metabolic disorders, such as obesity, cancer, inflammatory response, insulin resistance, and diabetes [ 5 , 7 , 8 , 9 , 10 ]. Many phytochemicals with metabolism-modulation effects have been proved to restore normal circadian rhythm in cell models and animal models, such as tea polyphenols, resveratrol, cichoric acid, and capsaicin [ 11 , 12 , 13 , 14 , 15 , 16 ]. Guo et al reported that cichoric acid could attenuate the lipid metabolism dysfunction by modulating the circadian gene Bmal1 expressions in hepatocytes [ 11 ].…”