Periostin promotes liver steatosis and hypertriglyceridemia through downregulation of PPARα

Abstract

Periostin neutralizing Ab. The hybridoma cell lines secreting mouse mAb against mouse periostin were generated by Abmart Co., according to the standard hybridoma technique (72). The mouse mAbs were purified by Protein A affinity chromatograph. mAb purity was confirmed by HPLC. The concentrations of the obtained mAbs were measured by Mouse IgG ELISA Quantitation kit (Bethyl Laboratories), following the manufacturer's instructions. The kinetic parameters of the mAbs were determined using a Biacore T100 instrument (Biacore AB). Purified Ab was diluted in saline and injected at a dose of 5 mg/kg into db/db mice for 2 weeks.Statistics. All values are shown as mean ± SEM. Statistical differences were determined by 2-way ANOVA with Bonferroni-adjusted post-test or by 2-tailed Student's t test. A P value less than 0.05 was considered significant.

Periostin on the road to nonalcoholic fatty liver disease

“…In line with experimental models, hepatic periostin expression and serum periostin levels were increased in NAFLD patients compared with controls [7]. Other authors also reported higher serum periostin levels in patients with acute or chronic hepatitis compared with controls; in the same study, periostin levels were well associated with TGF-b1 and TGF-b2 [9].…”

“…A eightfold higher hepatic periostin expression was shown in mice fed a high-fat diet compared with a chow diet [7]. Hepatic periostin was also markedly higher in ob/ob and db/db mice, known models of monogenic obesity and NAFLD, compared to lean controls [7]. Furthermore, overexpression of periostin in the liver of wild-type mice promoted hypertriglyceridemia and hepatic steatosis, possibly through reducing the expression of peroxisome proliferator-activated receptor (PPAR)-a pathway, thereby reducing fatty acid oxidation [7].…”

“…A eightfold higher hepatic periostin expression was shown in mice fed a high-fat diet compared with a chow diet [7]. Hepatic periostin was also markedly higher in ob/ob and db/db mice, known models of monogenic obesity and NAFLD, compared to lean controls [7].…”

“…Furthermore, overexpression of periostin in the liver of wild-type mice promoted hypertriglyceridemia and hepatic steatosis, possibly through reducing the expression of peroxisome proliferator-activated receptor (PPAR)-a pathway, thereby reducing fatty acid oxidation [7]. On the other hand, knockdown of periostin gene or administration of a periostin-neutralizing antibody in db/db mice reduced hepatic and serum triglycerides and improved steatosis, without affecting body weight, fat mass or transaminase levels [7].…”

Loss of periostin occurs in aging adipose tissue of mice and its genetic ablation impairs adipose tissue lipid metabolism

“…High‐fat feeding in mice induced Postn mRNA after a relatively short time course of 6 weeks, while the majority of our study participants had chronically established metabolic dysfunction including insulin resistance or type 2 diabetes, which could help explain this apparent discrepancy. In livers, Postn expression is elevated in obese mice and humans, and overexpression of periostin in mouse livers promoted hepatic steatosis and hypertriglyceridemia (Lu et al, 2014). These counteracting processes in liver and AT may explain the limited effects on plasma lipids and glucose metabolism and imply a tissue‐specific regulation and function of periostin.…”