Global Metabolic Profiling of Plasma Shows that Three-Year Mild-Caloric Restriction Lessens an Age-Related Increase in Sphingomyelin and Reduces L-leucine and L-phenylalanine in Overweight and Obese Subjects

Abstract

The effect of weight loss from long-term, mild-calorie diets (MCD) on plasma metabolites is unknown. This study was to examine whether MCD-induced weight reduction caused changes in the extended plasma metabolites. Overweight and obese subjects aged 4059 years consumed a MCD (approximately 100 kcal/day deficit, n=47) or a weight-maintenance diet (control, n=47) in a randomized, controlled design with a three-year clinical intervention period and plasma samples were analyzed by using UPLC-LTQ-Orbitrap mass spectrometry. The three-year MCD intervention resulted in weight loss (-8.87%) and significant decreases in HOMA-IR and TG. The three-year follow-up of the MCD group showed reductions in the following 13 metabolites: L-leucine; L-phenylalanine; 9 lysoPCs; PC (18:0/20:4); and SM (d18:0/16:1). The three-year MCD group follow-up identified increases in palmitic amide, oleamide, and PC (18:2/18:2). Considering the age-related alterations in the identified metabolites, the MCD group showed a greater decrease in L-leucine, L-phenylalanine, and SM (d18:0/16:1) compared with those of the control group. Overall, the change (△) in BMI positively correlated with the △TG, △HOMA-IR, △L-leucine, and △SM (d18:0/16:1). The △HOMA-IR positively correlated with △TG, △L-leucine, △L-phenylalanine, and △SM (d18:0/16:1). The weight loss resulting from three-year mildcaloric restriction lessens the age-related increase in SM and reduces L-leucine and L-phenylalanine in overweight and obese subjects. These changes were coupled with improved insulin resistance (ClinicalTrials.gov: NCT02081898).

Changes in Plasma Metabolite Concentrations after a Low‐Glycemic Index Diet Intervention

“…Conversely, glycine is a gluconeogenic amino acid, thus reduced levels may also reflect increased gluconeogenesis. Our findings regarding the modulation of leucine are in line with those from a previous weight‐loss intervention study that found that a mild‐caloric restriction diet for 3 years achieved weight loss, HOMA‐IR and TG reduction, and also improved a set of plasma metabolites, such as reducing leucine . There are emerging evidences supporting a role of BCAA in adipocyte differentiation and adipose tissue expansion since differences in leucine and valine metabolism have been shown between 3T3‐L1 preadipocytes and 3T3‐L1 adipocytes .…”

Changes in Serum Sphingomyelin After Roux-en-Y Gastric Bypass Surgery Are Related to Diabetes Status

“…Previous studies have reported a decreased serum or plasma sphingomyelin concentration after weight loss in humans ( 34 , 35 ). We could not confirm any linear relationship between sphingomyelin and body weight in all our patients, except for weak correlations at 12 and 24 months after surgery, where a higher body weight was associated to a lower sphingomyelin concentration.…”

Calorie restriction and its impact on gut microbial composition and global metabolism

“…Glyceryl derivatives of lipids and phospholipid choline in liver [60] and serum [16,71] were significantly decreased after CR intervention, such as phosphatidylcholine (PC) (18:0/20:4), sphingomyelin (SM) (d18:0/16:1), and some lysoPCs (C16:1, C16:0, C17:0, C18:2, C18:1, C18:0, C20:4, C20:3, and C22:6). Many of these compounds are involved in fatty acid catabolism, where triacylglycerols and phospholipids become hydrolyzed into non-esterified fatty acids, glycerol, and phosphocholine [67].…”

“…CR with its health-beneficial and lifespanextending effects has been applied and studied in such diverse species as fish, hamsters, mice, rats, and dogs [3,[8][9][10][11][12]. Likewise, CR-induced beneficial effects have been observed in nonhuman primates and humans [13][14][15][16]. Recently, knowledge of gut microbiota and metabolic changes that result from CR has substantially increased.…”