L-Serine Supplementation Blunts Fasting-Induced Weight Regain by Increasing Brown Fat Thermogenesis.

Weight regain after fasting, often exceeding the pre-fasting weight, is a common phenomenon and big problem for the treatment of obesity. Thus, novel interventions maintaining reduced body weight are critically important to prevent metabolic disease. Here we investigate the metabolic effects of dietary L-serine supplementation, known to modulate various organ functions. C57BL/6N-Rj male mice were supplemented with or without 1% L-serine in their drinking water and fed with a chow or high-fat diet. Mice were fed either ad libitum or subjected to repeated overnight fasting. Body weight, body composition, glucose tolerance and energy metabolism were assessed. This was combined with a detailed analysis of the liver and adipose tissues, including the use of primary brown adipocytes to study mitochondrial respiration and protein expression. We find that L-serine supplementation has little impact on systemic metabolism in ad libitum-fed mice. Conversely, L-serine supplementation blunted fasting-induced body weight regain, especially in diet-induced obese mice. This reduction in body weight regain is likely due to the increased energy expenditure, based on elevated brown adipose tissue activity. Thus, L-serine supplementation during and after weight-loss could reduce weight regain and thereby help tackle one of the major problems of current obesity therapies.

Effects of LC-PUFA supply via complementary food on infant development-a food based intervention (RCT) embedded in a total diet concept.

BACKGROUND: With the introduction of complementary food, long-chain PUFA (LC-PUFA) supply usually decreases during the second 6 months of life. However, the need for LC-PUFA is still high for infant's rapid development. The aim of this randomized, controlled intervention trial was to examine the effects of an increased n-3 (LC-)PUFA supply using alternative complementary foods on infants' visual and cognitive development. METHODS: Mother-child dyads of term infants were recruited in maternity hospitals and randomly assigned to one of three study groups, which all were fed according to the German dietary schedule for infant nutrition. Intervention group IG-R (n = 54) received jars of complementary food with rapeseed oil, IG-F (n = 48) jars with oily fish twice a week and the control group (CG, n = 58) the same jars as IG-R with corn oil instead of rapeseed oil during the intervention period (5th-10th month of age). The outcome measures were latencies of FVEP, Bayley's mental developmental index (MDI), and psychomotor developmental index (PDI). RESULTS: At 10 months of age, there were no significant differences in latencies of FVEP, Bayley's MDI, or in PDI index between the intervention and control groups. CONCLUSIONS: Fish and rapeseed oil used as (LC-)PUFA sources provided with complementary feeding embedded in a structured infant diet did not affect visual or cognitive development of term infants.

Chronic d-serine supplementation impairs insulin secretion.

OBJECTIVE: The metabolic role of d-serine, a non-proteinogenic NMDA receptor co-agonist, is poorly understood. Conversely, inhibition of pancreatic NMDA receptors as well as loss of the d-serine producing enzyme serine racemase have been shown to modulate insulin secretion. Thus, we aim to study the impact of chronic and acute d-serine supplementation on insulin secretion and other parameters of glucose homeostasis. METHODS: We apply MALDI FT-ICR mass spectrometry imaging, NMR based metabolomics, 16s rRNA gene sequencing of gut microbiota in combination with a detailed physiological characterization to unravel the metabolic action of d-serine in mice acutely and chronically treated with 1% d-serine in drinking water in combination with either chow or high fat diet feeding. Moreover, we identify SNPs in SRR, the enzyme converting L-to d-serine and two subunits of the NMDA receptor to associate with insulin secretion in humans, based on the analysis of 2760 non-diabetic Caucasian individuals. RESULTS: We show that chronic elevation of d-serine results in reduced high fat diet intake. In addition, d-serine leads to diet-independent hyperglycemia due to blunted insulin secretion from pancreatic beta cells. Inhibition of alpha 2-adrenergic receptors rapidly restores glycemia and glucose tolerance in d-serine supplemented mice. Moreover, we show that single nucleotide polymorphisms (SNPs) in SRR as well as in individual NMDAR subunits are associated with insulin secretion in humans. CONCLUSION: Thus, we identify a novel role of d-serine in regulating systemic glucose metabolism through modulating insulin secretion.