Methionine restriction effects on 11β-HSD1 activity and lipogenic/lipolytic balance in F344 rat adipose tissue

Abstract

Methionine restriction (MR) limits age-related adiposity in Fischer 344 (F344) rats. To assess the mechanism of adiposity resistance, the effect of MR on adipose tissue (AT) 11b-hydroxysteroid dehydrogenase-1 (11b-HSD1) was examined. MR induced 11b-HSD1 activity in all ATs, correlating with increased tissue corticosterone. However, an inverse relationship between 11b-HSD1 activity and adipocyte size was observed. Because dietary restriction controls lipogenic and lipolytic rates, MR's effects on lipogenic and lipolytic enzymes were evaluated. MR increased adipose triglyceride lipase and acetyl-coenzyme A carboxylase (ACC) protein levels but induced ACC phosphorylation at serine residues that render the enzyme inactive, suggesting alterations of basal lipolysis and lipogenesis. In contrast, no changes in basal or phosphorylated hormone-sensitive lipase levels were observed. ACCphosphorylated sites were specific for AMP-activated protein kinase (AMPK); therefore, AMPK activation was evaluated. Significant differences in AMPKa protein, phosphorylation, and activity levels were observed only in retroperitoneal fat from MR rats. No differences in protein kinase A phosphorylation and intracellular cAMP levels were detected. In vitro studies revealed increased lipid degradation and a trend toward increased lipid synthesis, suggesting the presence of a futile cycle. In conclusion, MR disrupts the lipogenic/lipolytic balance, contributing importantly to adiposity resistance in F344 rats.-Perrone, C.

Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states

“…For example, our studies illustrate that dietary MR alters endocrine function of WAT such that serum leptin and adiponectin are reciprocally affected. While the reduction in serum leptin is consistent with the hyperphagic response to MR, the acute three-fold increase in serum adiponectin observed here and before (25,29) suggests it as a potential mediator. For example, adiponectin activates AMPK in peripheral tissues (38,(41)(42)(43) and stimulates fatty acid oxidation while increasing glucose uptake.…”

“…Central and peripheral administration of adiponectin also increased EE and decreased body weight (30). The hypothesis that adiponectin may be a mediator of the diet is supported by recent work from our group showing coordinated increases in circulating adiponectin and activation of AMPK in retroperitoneal WAT (29). It will be important in future studies to examine whether adiponectin is required and antecedent to the increase in EE produced by the diet.…”

“…Pair-feeding studies comparing rats fed the control diet to the amount of MR diet consumed by the MR group clearly show that dietary MR decreases metabolic efficiency (25,46), but the underlying basis for the metabolic responses to dietary MR remains poorly understood. Short-(12 wk) and long-term (80 wk) consumption of the MR diet after weaning also reduced circulating triglyceride, insulin, and leptin while increasing plasma adiponectin (25,29). Collectively, work to date makes a compelling case that limitation of fat deposition by dietary MR is associated with preservation of insulin sensitivity and significant improvements in metabolic markers of lipid metabolism.…”

Genomic and Metabolic Responses to Methionine-Restricted and Methionine-Restricted, Cysteine-Supplemented Diets in Fischer 344 Rat Inguinal Adipose Tissue, Liver and Quadriceps Muscle

“…Significant reductions in body weight gain, adiposity and dyslipidemia as well as improvement of insulin sensitivity in rodents are hallmarks of MR [3,4]. Insulin sensitivity in MR rats is associated with reduced fat accretion, a response involving metabolic adaptations that alter lipid metabolism [4].…”

“…Significant reductions in body weight gain, adiposity and dyslipidemia as well as improvement of insulin sensitivity in rodents are hallmarks of MR [3,4]. Insulin sensitivity in MR rats is associated with reduced fat accretion, a response involving metabolic adaptations that alter lipid metabolism [4]. Decreased adiposity is also associated with increased energy expenditure [3,5] corresponding with the upregulation of peroxisome proliferator-activated receptor γ (PPARγ), PPARγ coactivator 1α (PGC1a) and their target genes, which leads to mitochondrial biogenesis in adipose tissues and increased mitochondrial aerobic capacity of liver and quadriceps muscle from MR rats [6].…”