Activation of peroxisome proliferator‐activated receptor‐α stimulated lipid catabolism in liver of largemouth bass, Micropterus salmoides

Abstract Objectives Sargassum serratifolium, a marine brown alga consumed in Asian countries, has shown anti-obesity effect by stimulating white adipose tissue browning. Therefore, the purpose of this study was to investigate lipid catabolic effects of sargahydroquinoic acid (SHQA), which is one of the major bioactive compounds of S. serratifolium by white adipocyte browning effect. Methods Isolated and purified SHQA from S. serratifolium was used to treat 3T3-L1 preadipocytes to see the effects of lipid catabolism and white adipocyte browning. Glycerol concentration measurement, Oil Red O lipid staining, and triglyceride quantification were conducted to examine the lipid catabolism by SHQA in the 3T3-L1 cells. In addition, real-time PCR and Western Blot assays were used to examine the expressions of genes related with lipid catabolic pathway, mitochondria biogenesis and white adipocyte browning. Results SHQA significantly upregulated non-shivering thermogenic gene expressions in 3T3-L1 cells including uncoupling protein 1, peroxisome proliferator-activated receptor γ and PR domain containing 16. SHQA also notably reduced cellular lipid accumulation. Interestingly, peroxisome proliferator-activated receptor (PPAR)γ, which is involved in lipid uptake and adipogenesis was upregulated by SHQA treatment. However, Western Blotting and protein-ligand docking simulation revealed that SHQA activates not only PPARγ but also PPARα and AMP-activated protein kinase (AMPK) α, which are lipid-catabolic proteins. In addition, SHQA treatment markedly elevated lipolysis and the amounts of mitochondria in 3T3-L1 cells. Conclusions Our results indicate that SHQA may combat obesity and associated metabolic syndromes through lipid catabolic pathways, mitochondria biogenesis and adipocyte browning by activating PPARγ, PPARα, and AMPKα pathways. Funding Sources This study was a part of the project, “Development of functional food products with natural materials derived from marine resources” funded by the Ministry of Oceans and Fisheries, Republic of Korea.

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Ethanol withdrawal mitigates fatty liver by normalizing lipid catabolism

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00376.2018 ◽

2019 ◽

Vol 316 (4) ◽

pp. G509-G518 ◽

Cited By ~ 6

Author(s):

Paul G. Thomes ◽

Karuna Rasineni ◽

Li Yang ◽

Terrence M. Donohue ◽

Jacy L. Kubik ◽

...

Keyword(s):

Transcription Factor ◽

Fatty Liver ◽

Control Diet ◽

Lipid Peroxides ◽

Ethanol Withdrawal ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Lipid Catabolism ◽

Transcription Factor Eb ◽

Nuclear Levels

We are investigating the changes in hepatic lipid catabolism that contribute to alcohol-induced fatty liver. Following chronic ethanol (EtOH) exposure, abstinence from alcohol resolves steatosis. Here, we investigated the hepatocellular events that lead to this resolution by quantifying specific catabolic parameters that returned to control levels after EtOH was withdrawn. We hypothesized that, after its chronic consumption, EtOH withdrawal reactivates lipid catabolic processes that restore lipostasis. Male Wistar rats were fed control and EtOH liquid diets for 6 wk. Randomly chosen EtOH-fed rats were then fed control diet for 7 days. Liver triglycerides (TG), lipid peroxides, key markers of fatty acid (FA) metabolism, lipophagy, and autophagy were quantified. Compared with controls, EtOH-fed rats had higher hepatic triglycerides, lipid peroxides, and serum free fatty acids (FFA). The latter findings were associated with higher levels of FA transporters (FATP 2, 4, and 5) but lower quantities of peroxisome proliferator-activated receptor-α (PPAR-α), which governs FA oxidation. EtOH-fed animals also had lower nuclear levels of the autophagy-regulating transcription factor EB (TFEB), associated with lower hepatic lipophagy and autophagy. After EtOH-fed rats were refed control diet for 7 days, their serum FFA levels and those of FATPs fell to control (normal) levels, whereas PPAR-α levels rose to normal. Hepatic TG and malondialdehyde levels in EtOH-withdrawn rats declined to near control levels. EtOH withdrawal restored nuclear TFEB content, hepatic lipophagy, and autophagy activity to control levels. EtOH withdrawal reversed aberrant FA metabolism and restored lysosomal function to promote resolution of alcohol-induced fatty liver. NEW & NOTEWORTHY Here, using an animal model, we show mechanisms of reversal of fatty liver and injury following EtOH withdrawal. Our data indicate that reactivation of autophagy and lysosome function through the restoration of transcription factor EB contribute to reversal of fatty liver and injury following EtOH withdrawal.

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