Supplementation of Chitosan Alleviates High-Fat Diet-Enhanced Lipogenesis in Rats via Adenosine Monophosphate (AMP)-Activated Protein Kinase Activation and Inhibition of Lipogenesis-Associated Genes

Abstract

This study investigated the role of chitosan in lipogenesis in high-fat diet-induced obese rats. The lipogenesis-associated genes and their upstream regulatory proteins were explored. Diet supplementation of chitosan efficiently decreased the increased weights in body, livers, and adipose tissues in high-fat diet-fed rats. Chitosan supplementation significantly raised the lipolysis rate; attenuated the adipocyte hypertrophy, triglyceride accumulation, and lipoprotein lipase activity in epididymal adipose tissues; and decreased hepatic enzyme activities of lipid biosynthesis. Chitosan supplementation significantly activated adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and attenuated high-fat diet-induced protein expressions of lipogenic transcription factors (PPAR-γ and SREBP1c) in livers and adipose tissues. Moreover, chitosan supplementation significantly inhibited the expressions of downstream lipogenic genes (FAS, HMGCR, FATP1, and FABP4) in livers and adipose tissues of high-fat diet-fed rats. These results demonstrate for the first time that chitosan supplementation alleviates high-fat diet-enhanced lipogenesis in rats via AMPK activation and lipogenesis-associated gene inhibition.

Functional Comparison of High and Low Molecular Weight Chitosan on Lipid Metabolism and Signals in High-Fat Diet-Fed Rats

“…It may be due to the reduced dietary carbohydrates. Chiu et al (2015) have also observed the decreased blood TG levels in HF diet-fed rats that could be reversed by high-MW chitosan supplementation [41]. In the present study, we explored that HF diet feeding inhibited blood Angptl4 and hepatic ApoE and MTTP protein expressions and decreased the blood TG levels, which could be reversed by both high- and low-MW chitosan supplementations.…”

“…Lipolysis rate was measured as described previously [41]. Briefly, 0.2 g adipose tissues were minced and added into a N-tris-(hydroxymethyl)-methyl-2-aminoethanesulfonic acid (25 mM) buffer containing isoproterenol (1 μM).…”

“…LPL activity was determined as described previously [41]. The 0.1 g adipose tissues were minced and added into a Krebs-Ringer bicarbonate buffer (pH 7.4) containing 10 units/mL heparin for 60 min at 37 °C, and then samples were incubated with equal volume of p -nitrophenyl butyrate (2 mM).…”

Green tea polyphenols ameliorate non-alcoholic fatty liver disease through upregulating AMPK activation in high fat fed Zucker fatty rats

“…Among these, AMPK-mediated phosphorylation of target substrates plays a critical role in the regulation of hepatic lipogenesis[21]. The activity of AMPK is stimulated by insulin through promoting its phosphorylation at Thr172[29], subsequently, AMPK activation leads to phosphorylation of ACC1 at Ser79 and ACC2 at Ser221, causing a reduction in ACC activity that lowers malonyl-CoA from acetyl-CoA, which leads to decreased hepatic TG synthesis[30,31]. …”

“…In addition to suppression of de novo lipogenesis, increased AMPK activity associated with inactivation of ACC by GTP may prevent hepatic injury by increasing fatty acid oxidation. Several lines of studies have demonstrated that reduction in malonyl-CoA secondary to AMPKα1-mediated ACC inactivation enhance carnitine palmitoyltransferase I (CPT I) activity, which in turn, increases in mitochondrial fatty acid oxidation by increasing CPT I flux[29,32]. Thus, by enhancing AMPK activation, reduced hepatic TG in GTP treated rats is due, at least in part, to suppression of hepatic lipogenesis and fatty acid oxidation in the liver through upregulating AMPK activation.…”