Phytol stimulates the browning of white adipocytes through the activation of AMP-activated protein kinase (AMPK) α in mice fed high-fat diet

Abstract

Stimulating the browning of white adipocytes contributes to the restriction of obesity and related metabolic disorders. This study aimed to investigate the browning effects of phytol on mice inguinal subcutaneous white adipose tissue (iWAT) and explore the underlying mechanisms. Our results demonstrated that phytol administration decreased body weight gain and iWAT index, and stimulated the browning of mice iWAT, with the increased expression of brown adipocyte marker genes (UCP1, PRDM16, PGC1α, PDH, and Cyto C). In addition, phytol treatment activated the AMPKα signaling pathway in mice iWAT. In good agreement with the in vivo findings, the in vitro results showed that 100 μM phytol stimulated brown adipogenic differentiation and formation of brown-like adipocytes in the differentiated 3T3-L1 by increasing the mitochondria content and oxygen consumption, and promoting mRNA and/or protein expression of brown adipocyte markers (UCP1, PRDM16, PGC1α, PDH, Cyto C, Cidea and Elovl3) and beige adipocyte markers (CD137 and TMEM26). Meanwhile, phytol activated the AMPKα signaling pathway in the differentiated 3T3-L1. However, the inhibition of AMPKα with Compound C totally abolished phytol-stimulated brown adipogenic differentiation and formation of brown-like adipocytes. In conclusion, these results showed that phytol stimulated the browning of mice iWAT, which was coincident with the increased formation of brown-like adipocytes in the differentiated 3T3-L1, and appeared to be primarily mediated by the AMPKα signaling pathway. These data provided new insight into the role of phytol in regulating the browning of WAT and suggested the potential application of phytol as a nutritional intervention for the restriction of obesity and related metabolic disorders.

Phytanic acid activates PPARα to promote beige adipogenic differentiation of preadipocytes

“…Given our observation that PA increased the mRNA and protein levels of PGC1α, which is a key regulator of mitochondrial biogenesis regulator, we further analyzed mitochondriogenesis which was promoted by PA treatment. Consistently, AMPK was also activated, which is in agreement with the effect of phytol in the browning process [19]. This phenomenon suggests that phytol and its metabolite PA may share signal pathways to promote beige adipocyte differentiation.…”

“…miR-196a) could also have positive effects on the browning of WAT [12]. In addition, pharmacological and nutritional agents, such as resveratrol [13], retinoic acid [14], curcumin [15], berberine [16], cryptotanshinone [17], sulforaphane [18] and phytol [19], enhance WAT browning by activating brown adipocytes-related signaling pathways.…”

Isoorientin ameliorates lipid accumulation by regulating fat browning in palmitate-exposed 3T3-L1 adipocytes

“…A growing body of evidence shows that fat browning is a promising therapeutic strategy for combating human obesity and insulin resistance, because of its substantial energy-burning potential [ [26] , [27] , [28] ]. Activation of fat browning has been found to reverse obesity and insulin resistance in mice fed a high-fat diet [ 29 ].…”

Genome-Wide Identification and Characterization of Long Noncoding RNAs of Brown to White Adipose Tissue Transformation in Goats

“…In particular, HADHA , HADHB , CPT1A , and ECHS1 were regulated by several lncRNAs in cis . It is worth noting that many target genes were significantly enriched in the AMPK signaling pathway, which is a critical pathway for energy metabolism [62] and the browning of white adipocytes [63]. In addition, AMPK α1- and α2-subunit knockout reduced adipogenesis and thermogenic function in brown adipose tissue compared to wild-type mice [64,65].…”