Potato protease inhibitor II prevents obesity by inducing browning of white adipose tissue in mice via β₃ adrenergic receptor signaling pathway

Abstract

There are currently few effective and safe pharmacologic means for inducing beige adipogenesis in humans. This study highlights the role of potato protease inhibitor II (PPI II) in regulating the browning of adipose tissue. The in vitro results showed that PPI II increased the expression of the uncoupling protein 1 (UCP1) protein and gene and beige‐specific genes, including Cd137, Cited1, Tbx1, and Tmem26 in vitro. PPI II treatment for three months in diet‐induced obesity mice increased the levels of the UCP1 protein in white adipose tissue, causing elevated energy expenditure, thus preventing obesity and improving glucose tolerance. Mechanistic studies further revealed that PPI II regulated the abundance and activity of β3 adrenergic receptor (β3‐AR) in white adipocytes. Chemical‐inhibition experiments revealed the crucial role of β3‐AR‐dependent protein kinase A (PKA)‐p38 kinase (p38)/extracellular signal‐related kinase1/2 (ERK1/2) signaling in PPI II‐mediated browning program of white adipose tissues. In summary, our findings highlight the role of PPI II in beige adipocyte differentiation and thermogenesis and provide new insights into its use in preventing obesity.

Genistein protects against hyperglycemia and fatty liver disease in diet-induced prediabetes mice via activating hepatic insulin signaling pathway

“…Western blot was performed based on protocol published before ( 20 ). The protein lysates of liver were separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred to a polyvinylidene difluoride membrane.…”