Methionine restriction decreases visceral fat mass and preserves insulin action in aging male Fischer 344 rats independent of energy restriction

Abstract

SummaryReduced dietary methionine intake (0.17% methionine, MR) and calorie restriction (CR) prolong lifespan in male Fischer 344 rats. Although the mechanisms are unclear, both regimens feature lower body weight and reductions in adiposity. Reduced fat deposition in CR is linked to preservation of insulin responsiveness in older animals. These studies examine the relationship between insulin responsiveness and visceral fat in MR and test whether, despite lower food intake observed in MR animals, decreased visceral fat accretion and preservation of insulin sensitivity is not secondary to CR. Accordingly, rats pair fed (pf) control diet (0.86% methinone, CF) to match the food intake of MR for 80 weeks exhibit insulin, glucose, and leptin levels similar to control-fed animals and comparable amounts of visceral fat. Conversely, MR rats show significantly reduced visceral fat compared to CF and PF with concomitant decreases in basal insulin, glucose, and leptin, and increased adiponectin and triiodothyronine. Daily energy expenditure in MR animals significantly exceeds that of both PF and CF. In a separate cohort, insulin responses of older MR animals as measured by oral glucose challenge are similar to young animals. Longitudinal assessments of MR and CF through 112 weeks of age reveal that MR prevents age-associated increases in serum lipids. By 16 weeks, MR animals show a 40% reduction in insulin-like growth factor-1 (IGF-1) that is sustained throughout life; CF IGF-1 levels decline much later, beginning at 112 weeks. Collectively, the results indicate that MR reduces visceral fat and preserves insulin activity in aging rats independent of energy restriction.

Methionine Sulfoxide Reductase A and a Dietary SupplementS-Methyl-L-Cysteine Prevent Parkinson's-Like Symptoms

“…However, methionine is rapidly incorporated into protein, and it increases the plasma levels of homocysteine and cholesterol, which may be risk factors in cardiovascular diseases (Hirche et al, 2006). In fact, dietary methionine restriction, instead of supplementation, induces beneficial anti-aging effects (Malloy et al, 2006). Hence, the practical use of methionine supplementation in humans is probably doubtful.…”

Dietary Interventions to Extend Life Span and Health Span Based on Calorie Restriction

“…One study showed that methionine restriction results in decreased visceral fat deposition and preservation of insulin sensitivity, and these effects were not seen in pair-fed controls (117). Another study achieved consistent caloric intake among control and experimental animals through use of a methionine-depleted energy-dense diet and found that methionine restriction reduced body size regardless of equivalent caloric intake (123). These results suggest that growth impairment can be related to methionine intake and not solely calorie intake, but it still remains to be shown that methionine restriction independently of any CR effect results in life-span extension in rodents.…”

Food Restriction Ameliorates the Development of Polycystic Kidney Disease

“…28,32 Furthermore, a form of MR and IGF-1 suppression can be achieved in humans with the so-called vegan diet. 31 Interestingly, there are studies implicating protein load as an important factor in the development of ADPKD in animal models; however, studies on protein restriction in patients with renal failure and advanced ADPKD failed to show benefits, and indeed demonstrated a trend for increased morbidity with low protein intake. 33,34 In this regard, it is important for future studies to determine the specific role of calories and macronutrients in the effect of nutritional manipulations described in here.…”

“…It has also been shown that restriction of a single amino acid, namely methionine restriction (MR), can decrease IGF-1 levels and mimic several effects of FR. 31 In fact, MR extends life-span and metabolic health in several in vitro and animal models. 28,32 Furthermore, a form of MR and IGF-1 suppression can be achieved in humans with the so-called vegan diet.…”