The Impact of Dietary Methionine Restriction on Biomarkers of Metabolic Health

Abstract

Calorie restriction without malnutrition, commonly referred to as dietary restriction (DR), results in a well-documented extension of life span. DR also produces significant, long-lasting improvements in biomarkers of metabolic health that begin to accrue soon after its introduction. The improvements are attributable in part to the effects of DR on energy balance, which limit fat accumulation through reduction in energy intake. Accumulation of excess body fat occurs when energy intake chronically exceeds the energy costs for growth and maintenance of existing tissue. The resulting obesity promotes the development of insulin resistance, disordered lipid metabolism, and increased expression of inflammatory markers in peripheral tissues. The link between the life-extending effects of DR and adiposity is the subject of an ongoing debate, but it is clear that decreased fat accumulation improves insulin sensitivity and produces beneficial effects on overall metabolic health. Over the last 20 years, dietary methionine restriction (MR) has emerged as a promising DR mimetic because it produces a comparable extension in life span, but surprisingly, does not require food restriction. Dietary MR also reduces adiposity but does so through a paradoxical increase in both energy intake and expenditure. The increase in energy expenditure fully compensates for increased energy intake and effectively limits fat deposition. Perhaps more importantly, the diet increases metabolic flexibility and overall insulin sensitivity and improves lipid metabolism while decreasing systemic inflammation. In this chapter, we describe recent advances in our understanding of the mechanisms and effects of dietary MR and discuss the remaining obstacles to implementing MR as a treatment for metabolic disease.

A Methionine-Restricted Diet and Endurance Exercise Decrease Bone Mass and Extrinsic Strength but Increase Intrinsic Strength in Growing Male Rats

“…Although the mechanism or mechanisms by which MR decreases BW have not been yet identified, because Met is critical for normal growth and development and plays a key role in protein synthesis, DNA methylation, and polyamine synthesis (5), the MR effects appear to be a phenomenon that could be associated with reduced anabolism and development. In addition, mice fed CR diets had different gene expression patterns from those fed MR diets, implying that there are inherent differences between CR and MR (34,35).…”

“…An MR diet has been already translated to humans (35). In fact, fat oxidation significantly increased in obese adults who were administered a diet in which Met was limited to 2 mg/(kg Á d) (49).…”

The Mitochondrial Free Radical Theory of Aging

“…49 In addition to extending life-span, 80%MetR also decreases diseaseassociated markers and the incidence of age-related degenerative diseases. 50,51 The beneficial effects of this intervention in rodents include decreases in serum glucose, insulin, IGF1, cholesterol, triglycerides, and leptin. Besides, MetR protects against age-related changes in immunity, slows cataract development, 38 improves colon tight junction barrier function, 52 and improves metabolic flexibility and increases respiratory uncoupling.…”

Dietary Sulfur-Containing Amino Acids Are Associated with Higher Prevalence of Overweight/Obesity in Northern Chinese Adults, an Internet-Based Cross-Sectional Study

“…Cellular studies demonstrated cysteine auto-oxidation in human plasma releases H 2 O 2 [26], and H 2 O 2 inhibits hormone-sensitive lipase via disulphide modification within cAMP-dependent protein kinase A [27], which may thus result in lipid storage. Furthermore, Virtanen et al [28] found that methionine intake was positively associated with BMI and dietary methionine restriction-reduced adiposity [29], so methionine restriction has emerged as a promising treatment for obesity in recent years. Moreover, stearoyl-CoA desaturase-1 is a key enzyme in fatty acid and energy metabolism.…”