Methionine Restriction Partly Recapitulates the Sympathetically Mediated Enhanced Energy Expenditure Induced by Total Amino Acid Restriction in Rats

Abstract

Total amino acid (AA) restriction promotes hyperphagia and energy expenditure. We determined whether (i) methionine restriction mimics the effects of total AA restriction, (ii) methionine supplementation attenuates these responses, and iii) sympathetic signaling mediates such effects. Rats were injected with either vehicle (V) or 6-hydroxydopamine (S) to induce chemical sympathectomy, and then randomized to four diets: 16% AA (16AA), 5% AA (5AA), 16% AA-methionine (16AA-Met), and 5% AA+methionine (5AA+Met). Propranolol or ondansetron were injected to examine the role of sympathetic and serotonergic signaling, respectively. 5AA, 5AA+Met, and 16AA-Met increased the food conversion rate for 1–3 weeks in the V and S groups, and increased mean energy expenditure in V group,; the magnitude of these changes was attenuated in the S group. Propranolol decreased the energy expenditure of V16AA, V5AA, and V5AA+Met and of S5AA, S5AA+Met, and S16AA-Met, whereas ondansetron decreased the energy expenditure in only the S groups. Compared to 16AA, the other V groups had reduced body weights from days 7–11 onwards and decreased lean masses throughout the study and the other S groups had decreased body weights and lean masses from day 14 onwards. Total AA restriction enhanced the energy expenditure and reduced the weight and lean mass; these effects were partly recapitulated by methionine restriction and were sympathetically mediated.

Dietary Sulfur Amino Acid Restriction and the Integrated Stress Response: Mechanistic Insights

“…This SAAR-mediated increase in food consumption is reported on extensively in rodents [4,16,63]. Notably, while the increased energy expenditure seen in SAA restricted animals has been well-delineated and found to be, at least in part, dependent on a number of mechanisms including β-adrenergic signaling, the mechanisms behind the hyperphagic response have been less clear, but have been reported to partly depend of β-adrenergic signaling [64,65].…”

Effect of very low-protein diets supplemented with branched-chain amino acids on energy balance, plasma metabolomics and fecal microbiome of pigs

“…Statistical analysis was performed as we previously described 33 , 66 , 67 , 79 . General linear mixed model (IBM SPSS Statistics Version 23, Armonk, NY, USA) was used the analyze the daily and weekly measurements.…”

Protein, amino acids and obesity treatment

“…Methionine restriction in rodents reproduces the beneficial effects of total amino acid restriction, on body weight and composition, insulin sensitivity and sympathetically mediated energy expenditure. Compared to total amino acid restriction, methionine restriction can lead to either hyperphagia or transient hypophagia in diet induced obesity rodent models [87,88]. Methionine restriction improves glucose metabolism and insulin sensitivity in obese mice by a cross talk between the adipose tissue and skeletal muscle, involving an adipose-derived factor, the adiponectin.…”

“…To recapitulate , methionine restriction has positive effects on health, as seen in rodent models of diet-induced obesity and a human study reviewed here. Moreover, one fails to normalize metabolic responses in DIO rat models when moderately restricting protein but keeping the methionine levels at a correct level [ 87 ]. However, adding another sulfur amino acid, cysteine, can reverse the effects seen above in mice models concerning energy expenditure, weight gain, lipid, insulin and adiponectin plasmatic levels [ 90 , 100 ].…”