Pycnogenol Supplementation Promotes Lipolysis via Activation of cAMP-Dependent PKA in <i>ob/ob</i> Mice and Primary-Cultured Adipocytes

Abstract

Summary This study investigated the PKA-dependent inhibitory effect of pycnogenol (Pyc) on lipolysis using ob/ob mice and primary mouse adipocytes. Supplementation of Pyc at 30 mg/kg significantly reduced body weight gain and visceral fat mass. The serum and hepatic triglyceride (TG) and total cholesterol (TC) levels were reduced by Pyc supplementation, and high density lipoprotein (HDL)-cholesterol level significantly increased. In addition, hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) mRNA levels increased with Pyc supplementation in adipose tissue of ob/ob mice. The treatment of primary cultured adipocytes with Pyc at 100 mg/mL significantly increased glycerol release, cAMP level by reduction of phosphodiestersae-3B (PDE3B), and HSL levels, but decreased protein levels of perilipin A and fatty acid synthetase (FAS). The PKA inhibitor (H89) clearly blocked the cellular levels of perilipin A and HSL, suggesting that Pyc promotes lipolysis of adipocytes through activation of cAMP-dependent PKA, resulting in induction of HSL and reduction of perilipin A. Therefore, this study may elucidate the possible mechanism of Pyc, which is a candidate for weight loss through stimulation of lipolysis.

Pycnogenol protects against diet-induced hepatic steatosis in apolipoprotein-E-deficient mice

“…In this study, we evaluated the effects of PYC on hepatic steatosis and further explored the underlying mechanism in ApoE-deficient mice. Previous studies have shown that PYC effects the regulation of lipid metabolism and possesses protective effects on nonalcoholic steatohepatitis (5,18,38). In line with previous results, we found that PYC reduced body weight gain and decreased plasma lipid and hepatic lipid accumulation in ApoE-deficient mice.…”

“…Furthermore, intracellular lipolysis stimulates the breakdown of TGs stored in LDs for subsequent metabolism, and HSL is the rate-limiting enzyme in fat catabolic pathways in adipocytes as well as nonadipocytes. Previous studies have shown that PYC promotes lipolysis in adipocytes (18). We found that the expression of the HSL gene was increased in the liver after supplementation with PYC.…”

“…Meanwhile, an openlabel controlled study has shown that the supplementation of PYC in 130 subjects with symptoms of metabolic syndrome decreases waist circumference and TG levels and increases HDL levels (5). It has been reported that PYC is involved in lipid metabolism and has a protective capacity against hepatotoxicity and oxidative stress in the livers of mice (18,38,44). The phenols and polyphenols, as the main ingredient of PYC, have been shown to improve hepatic steatosis, including apple polyphenols, resveratrol, polyphenol-rich grape skin extract, and others (3,28,42,54,56).…”

Indirubin, a small molecular deriving from connectivity map (CMAP) screening, ameliorates obesity-induced metabolic dysfunction by enhancing brown adipose thermogenesis and white adipose browning

“…It has been proved that increased PKA activity specifically in adipose tissue could upregulate UCP1 expression and ameliorate metabolism discords. PKA activates p38 MAPK and increases the expression of UCP1, thereby promoting thermogenesis in BAT [75,76]. Moreover, increased PKA activity has also been linked to induction of browning in sWAT [77,78].…”

The impact of pycnogenol supplementation on plasma lipids in humans: A systematic review and meta‐analysis of clinical trials

“…It might act through increasing the concentration of hormone sensitive lipase and adipose triglyceride lipase in adipose tissue. Also, it can promote lipolysis by decreasing the activity of prilipin A and fatty acid synthetase (Ho, Kim, Nam, Jun, & Lee, ). Pycnogenol reduces LDL‐C concentration via inhibiting cholesterol biosynthesis, upregulating hepatic LDL‐C receptor and increasing sterol excretion (Kurowska et al, ).…”