Dietary Phosphorus Reduced Hepatic Lipid Deposition by Activating Ampk Pathway and Beclin1 Phosphorylation Levels to Activate Lipophagy in Tilapia Oreochromis niloticus

Abstract

High-phosphorus diet (HPD) reduces lipid deposition and significantly influences lipid metabolism. However, the relevant mechanism is unknown. Herein, using widely-cultured teleost tilapia Oreochromis niloticus as the experimental animals, we found that HPD and Pi incubation reduced triglyceride (TG) content (P ≤ 0.05), suppressed lipogenesis, activated AMP-activated protein kinase (AMPK) pathway and autophagy (P ≤ 0.05), and increased fatty acid β-oxidation and lipolysis in tilapia liver and hepatocytes (P ≤ 0.05). Our further investigation indicated that Pi treatments activated the lipophagy and facilitated mitochondrial fatty acid β-oxidation, and according reduced TG deposition (P ≤ 0.05). Mechanistically, phosphorus increased the AMPKα1 phosphorylation level at S496 and Beclin1 phosphorylation at S90, and Beclin1 phosphorylation by AMPKα1 was required for phosphorus-induced lipophagy and lipolysis. Our study revealed a mechanism for Beclin1 regulation and autophagy induction in response to high-phosphorus diet, and provided novel evidences for the link between dietary phosphorus addition and lipolytic metabolism via the AMPK/Beclin1 pathway. Our results also suggested that AMPK should be the potential target for the prevention and control of lipid metabolic disorders. Overall, these results suggested that HPD reduced hepatic lipid deposition by activating AMPK pathway and Beclin1 phosphorylation levels to activate lipophagy, which provided potential targets for the prevention and control of fatty liver in fish.

Neohesperidin Dihydrochalcone Ameliorates High-Fat Diet-Induced Glycolipid Metabolism Disorder in Rats

“…Therefore, the TLR4/Myd88/NF-κB pathway is involved in the regulation of NHDC on HFD-induced inflammation of ileum. AMPK and PGC-1α are key regulators of energy metabolism and play important roles in various energy metabolism processes. , SIRT1 is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase in regulating the expression of glucose and lipid metabolism related proteins. − AMPK is an important energy sensor involved in maintaining the balance of energy metabolism . Our results suggest that NHDC regulates glycolipid metabolism disorder through the AMPK/SIRT1/PGC-1α pathway.…”

“…AMPK and PGC-1α are key regulators of energy metabolism and play important roles in various energy metabolism processes. 43,44 SIRT1 is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase in regulating the expression of glucose and lipid metabolism related proteins. 45−47 AMPK is an important energy sensor involved in maintaining the balance of energy metabolism.…”

Klf4-Sirt3/Pparα-Lcad pathway contributes to high phosphate-induced lipid degradation

“…To explore the underlying mechanisms for Pi-induced lipolysis, we constructed the Klf4, Sirt3, Lcad, Errα and Pgc1α expression vectors based on the published protocols [ 12 ]. We subcloned the open reading frames (ORFs) of Sirt3 and Pgc1α sequences into the pcDNA3.1 (+) vector with the HA-tag at the N-terminus, respectively.…”

“…Western blot analysis was conducted to explore the protein expression of Slc34a2, Ucp2, Klf4, Sirt3, Pparα and Lcad, based on the protocols in Liu et al [ 12 ]. In brief, intestinal tissues and primary IECs samples were homogenized in ice-cold radioimmunoprecipitation assay buffer (Thermo Fisher Scientific, USA) supplemented with protease and deacetylase inhibitors (Roche, Indianapolis, IN, USA).…”

“…Chun et al [ 11 ] pointed out that dietary Pi excess promotes energy expenditure via the fatty acid β-oxidation in the liver. Liu et al [ 12 ] found that dietary phosphate reduced lipid deposition in the liver by activating Ampk pathway. However, at present, the mechanism of dietary phosphate affecting mitochondrial fatty acid oxidation is unclear in the intestine.…”