Pycnogenol® Induces Browning of White Adipose Tissue through the PKA Signaling Pathway in Apolipoprotein E-Deficient Mice

Abstract

Beige adipocytes in white adipose tissue (WAT) have received considerable recognition because of their potential protective effect against obesity. Pycnogenol (PYC), extracted from French maritime pine bark, has anti-inflammatory and antioxidant properties and can improve lipid profiles. However, the effect of PYC on obesity has never been explored. In this study, we investigated the effects of PYC on obesity and WAT browning in apolipoprotein E- (ApoE-) deficient mice. The results showed that PYC treatment clearly reversed body weight and the mass of eWAT gain resulting from a high-cholesterol and high-fat diet (HCD), but no difference in food intake. The morphology results showed that the size of the adipocytes in the PYC-treated mice was obviously smaller than that in the HCD-fed mice. Next, we found that PYC upregulated the expression of genes related to lipolysis (ATGL and HSL), while it decreased the mRNA level of PLIN1. PYC significantly increased the expression of UCP1 and other genes related to beige adipogenesis. Additionally, PYC increased the expression of proteins related to the protein kinase A (PKA) signaling pathway. The findings suggested that PYC decreased obesity by promoting lipolysis and WAT browning. Thus, PYC may be a novel therapeutic target for obesity.

Activation of AMP-Activated Protein Kinase-Sirtuin 1 Pathway Contributes to Salvianolic Acid A-Induced Browning of White Adipose Tissue in High-Fat Diet Fed Male Mice

“…Cold exposure is a wellestablished effective way to stimulate adipose tissue thermogenesis. Several pathways have been identified to contribute to cold exposure-induced UCP-1 expression and subsequent WAT browning (Liu et al, 2019), among which, AMP-activated protein kinase (AMPK) (Lee et al, 2020), sirtuin 1 (SIRT1) (Liao et al, 2018), and protein kinase A (PKA) (Cong et al, 2018) stimulate, while p38 mitogen-activated protein kinase (MAPK) inhibits, white adipose tissue browning (Wang et al, 2019). Obesity adversely impacts these signaling pathways, contributing to defective WAT browning in HFD-induced obesity (Zhang et al, 2019).…”

Flavonoid‐enriched extract from Millettia speciosa Champ prevents obesity by regulating thermogenesis and lipid metabolism in high‐fat diet–induced obese C57BL/6 mice

“…BAT consumes energy by oxidizing fatty acids to generate heat (Qurania et al., 2018). Importantly, browning of WAT promotes energy expenditure through triggering thermogenesis, which suppresses high‐fat diet (HFD)–induced weight gain (Bi et al., 2014; Cong et al., 2018). The current research suggests that browning of WAT might serve as a novel strategy for the prevention of obesity (Baskaran et al., 2016; Guan et al., 2018).…”

The Gintonin-Enriched Fraction of Ginseng Regulates Lipid Metabolism and Browning via the cAMP-Protein Kinase a Signaling Pathway in Mice White Adipocytes

“…Activation of the cAMP-dependent pathway, which involves the phosphorylation of PKA, stimulates lipolysis by activating both adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), which hydrolyze TGs in the lipid droplets of white adipocytes [8,9]. The released free fatty acids can undergo mitochondrial β-oxidation [10], which generates acetyl CoA that is required for WAT browning. Indeed, a recent study showed that PKA activation upregulates UCP1 expression in beige adipocytes [11].…”