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Remodeling the integration of lipid metabolism between liver and adipose tissue by dietary methionine restriction in rats.

ABSTRACT: Dietary methionine restriction (MR) produces an integrated series of biochemical and physiological responses that improve biomarkers of metabolic health, limit fat accretion, and enhance insulin sensitivity. Using transcriptional profiling to guide tissue-specific evaluations of molecular responses to MR, we report that liver and adipose tissue are the primary targets of a transcriptional program that remodeled lipid metabolism in each tissue. The MR diet produced a coordinated downregulation of lipogenic genes in the liver, resulting in a corresponding reduction in the capacity of the liver to synthesize and export lipid. In contrast, the transcriptional response in white adipose tissue (WAT) involved a depot-specific induction of lipogenic and oxidative genes and a commensurate increase in capacity to synthesize and oxidize fatty acids. These responses were accompanied by a significant change in adipocyte morphology, with the MR diet reducing cell size and increasing mitochondrial density across all depots. The coordinated transcriptional remodeling of lipid metabolism between liver and WAT by dietary MR produced an overall reduction in circulating and tissue lipids and provides a potential mechanism for the increase in metabolic flexibility and enhanced insulin sensitivity produced by the diet.

SUBMITTER: Hasek BE

PROVIDER: S-EPMC3781441 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Remodeling the integration of lipid metabolism between liver and adipose tissue by dietary methionine restriction in rats.

Hasek Barbara E BE Boudreau Anik A Shin Jeho J Feng Daorong D Hulver Matthew M Van Nancy T NT Laque Amanda A Stewart Laura K LK Stone Kirsten P KP Wanders Desiree D Ghosh Sujoy S Pessin Jeffrey E JE Gettys Thomas W TW

Diabetes 20130625 10

Dietary methionine restriction (MR) produces an integrated series of biochemical and physiological responses that improve biomarkers of metabolic health, limit fat accretion, and enhance insulin sensitivity. Using transcriptional profiling to guide tissue-specific evaluations of molecular responses to MR, we report that liver and adipose tissue are the primary targets of a transcriptional program that remodeled lipid metabolism in each tissue. The MR diet produced a coordinated downregulation of ...[more]

PMID: 23801581

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Project description:BackgroundHigh dietary protein can reduce fat deposition in animal subcutaneous adipose tissue, but little is known about the mechanism.MethodsSixty Wujin pigs of about 15 kg weight were fed either high protein (HP: 18%) or low protein (LP: 14%) diets, and slaughtered at body weights of 30, 60 or 100 kg. Bloods were collected to measure serum parameters. Subcutaneous adipose tissues were sampled for determination of adipocyte size, protein content, lipid metabolism-related gene expression, and enzyme activities.ResultsHP significantly reduced adipocyte size, fat meat percentage and backfat thickness, but significantly increased daily gain, lean meat percentage and loin eye area at 60 and 100 kg. Serum free fatty acid and triglyceride concentrations in the HP group were significantly higher than in the LP group. Serum glucose and insulin concentrations were not significantly affected by dietary protein at any body weight. HP significantly reduced gene expression of acetyl CoA carboxylase (ACC), fatty acid synthase (FAS) and sterol regulatory element binding protein 1c (SREBP-1c) at 60 kg and 100 kg; however, the mRNA level and enzyme activity of FAS were increased at 30 kg. HP promoted gene and protein expression and enzyme activities of lipoprotein lipase (LPL), carmitine palmtoyltransferase-1B (CPT-1B), peroxisome proliferator-activated receptor gamma (PPARgamma) and adipocyte-fatty acid binding proteins (A-FABP) at 60 kg, but reduced their expression at 100 kg.Gene expression and enzyme activity of hormone sensitive lipase (HSL) was reduced markedly at 60 kg but increased at 100 kg by the high dietary protein. Levels of mRNA, enzyme activities and protein expression of ACC, FAS, SREBP-1c and PPARgamma in both LP and HP groups increased with increasing body weight. However, gene and protein expression levels/enzyme activities of LPL, CPT-1B, A-FABP and HSL in both groups were higher at 60 kg than at 30 and 100 kg.ConclusionFat deposition in Wujin pigs fed high dietary protein for 25 weeks was reduced mainly by depression of lipogenic gene expression. The mechanism of lipid transport, lipolysis and oxidation in adipose tissue regulated by dietary protein appeared to be different at 60 kg and 100 kg body weights.

Project description:Methionine is a rate-limiting amino-acid for protein synthesis but non-proteinogenic roles on lipid metabolism and oxidative stress have been demonstrated. Contrary to rodents where a dietary methionine deficiency led to a lower adiposity, an increased lipid accretion rate has been reported in growing pigs fed a methionine deficient diet. This study aimed to clarify the effects of a dietary methionine deficiency on different aspects of tissue lipid metabolism and anti-oxidant pathways in young pigs. Post-weaned pigs (9.8 kg initial body weight) were restrictively-fed diets providing either an adequate (CTRL) or a deficient methionine supply (MD) during 10 days (n=6 per group). At the end of the feeding trial, pigs fed the MD diet had higher lipid content in subcutaneous adipose tissue. Expression levels of genes involved in glucose uptake, lipogenesis but also lipolysis, and activities of NADPH enzyme suppliers were generally higher in subcutaneous and perirenal adipose tissues of MD pigs, suggesting an increased lipid turnover in those pigs. Activities of the anti-oxidant enzymes superoxide dismutase, catalase and glutathione reductase were increased in adipose tissues and muscle of MD pigs. Expression level and activity of the glutathione peroxidase were also higher in liver of MD pigs, but hepatic contents in the reduced and oxidized forms of glutathione and glutathione reductase activity were lower compared with control pigs. In plasma, superoxide dismutase activity was higher but total anti-oxidant power was lower in MD pigs. These results show that a dietary methionine deficiency resulted in increased levels of lipogenesis and lipolytic indicators in porcine adipose tissues. Decreased glutathione content in the liver and coordinated increase of enzymatic antioxidant activities in adipose tissues altered the cellular redox status of young pigs fed a methionine-deficient diet. These findings illustrate that a rapidly growing animal differently adapts tissue metabolisms when facing an insufficient methionine supply.

Project description:BackgroundIn mammals, the nutritional status experienced during embryonic development shapes key metabolic pathways and influences the health and phenotype of the future individual, a phenomenon known as nutritional programming. In farmed birds as well, the quantity and quality of feed offered to the dam can impact the phenotype of the offspring. We have previously reported that a 38% reduction in the intake of the methyl donor methionine in the diet of 30 female ducks during the growing and laying periods - from 10 to 51 weeks of age - reduced the body weight of their 180 mule ducklings compared to that of 190 ducklings from 30 control females. The maternal dietary methionine restriction also altered the hepatic energy metabolism studied in 30 of their ducklings. Thus, their plasma glucose and triglyceride concentrations were higher while their plasma free fatty acid level was lower than those measured in the plasma of 30 ducklings from the control group. The objective of this new study was to better understand how maternal dietary methionine restriction affected the livers of their newly hatched male and female ducklings by investigating the hepatic expression levels of 100 genes primarily targeting energy metabolism, amino acid transport, oxidative stress, apoptotic activity and susceptibility to liver injury.ResultsSixteen of the genes studied were differentially expressed between the ducklings from the two groups. Maternal dietary methionine restriction affected the mRNA levels of genes involved in different pathways related to energy metabolism such as glycolysis, lipogenesis or electron transport. Moreover, the mRNA levels of the nuclear receptors PPARGC1B, PPARG and RXRA were also affected.ConclusionsOur results show that the 38% reduction in methionine intake in the diet of female ducks during the growing and egg-laying periods impacted the liver transcriptome of their offspring, which may explain the previously observed differences in their liver energy metabolism. These changes in mRNA levels, together with the observed phenotypic data, suggest an early modulation in the establishment of metabolic pathways.

Dataset Information

Remodeling the integration of lipid metabolism between liver and adipose tissue by dietary methionine restriction in rats.

Publications

Remodeling the integration of lipid metabolism between liver and adipose tissue by dietary methionine restriction in rats.

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