Lactate is a potential energy source for the brain. The aim of this study was to establish whether systemic lactate is a brain energy source. We measured in vivo cerebral lactate kinetics and oxidation rates in 6 healthy individuals at rest with and without 90 mins of intravenous lactate infusion (36 mumol per kg bw per min), and during 30 mins of cycling exercise at 75% of maximal oxygen uptake while the lactate infusion continued to establish arterial lactate concentrations of 0.89+/-0.08, 3.9+/-0.3, and 6.9+/-1.3 mmol/L, respectively. At rest, cerebral lactate utilization changed from a net lactate release of 0.06+/-0.01 to an uptake of 0.16+/-0.07 mmol/min during lactate infusion, with a concomitant decrease in the net glucose uptake. During exercise, the net cerebral lactate uptake was further increased to 0.28+/-0.16 mmol/min. Most (13)C-label from cerebral [1-(13)C]lactate uptake was released as (13)CO(2) with 100%+/-24%, 86%+/-15%, and 87%+/-30% at rest with and without lactate infusion and during exercise, respectively. The contribution of systemic lactate to cerebral energy expenditure was 8%+/-2%, 19%+/-4%, and 27%+/-4% for the respective conditions. In conclusion, systemic lactate is taken up and oxidized by the human brain and is an important substrate for the brain both under basal and hyperlactatemic conditions.

In a sheep model, we investigated diet effects on skeletal muscle mitochondria to look for fetal programming. During pregnancy, ewes were fed normally (N) or were 50% food restricted (L) during the last trimester, and lambs born to these ewes received a normal (N) or a high-fat diet (H) for the first 6 mo of life. We examined mitochondrial function in permeabilized muscle fibers from the lambs at 6 mo of age (adolescence) and after 24 mo of age (adulthood). The postpartum H diet for the lambs induced an ϳ30% increase (P Ͻ 0.05) of mitochondrial V O2max and an ϳ50% increase (P Ͻ 0.05) of the respiratory coupling ratio (RCR) combined with lower levels of UCP3 and PGC-1␣ mRNA levels (P Ͻ 0.05). These effects proved to be reversible by a normal diet from 6 to 24 mo of age. However, at 24 mo, a long-term effect of the maternal gestational diet restriction (fetal programming) became evident as a lower V O2max (ϳ40%, P Ͻ 0.05), a lower state 4 respiration (ϳ40%, P Ͻ 0.05), and lower RCR (ϳ15%, P Ͻ 0.05). Both PGC-1␣ and UCP3 mRNA levels were increased (P Ͻ 0.05). Two analyzed muscles were affected differently, and muscle rich in type I fibers was more susceptible to fetal programming. We conclude that fetal programming, seen as a reduced V O2max in adulthood, results from gestational undernutrition. Postnatal high-fat diet results in a pronounced RCR and V O2max increase in adolescence. However, these effects are reversible by diet correction and are not maintained in adulthood. metabolic syndrome; high-fat diet; nutrient restriction; maternal diet; respiratory coupling ratio EPIDEMIOLOGICAL STUDIES IN HUMANS since the 1980s and subsequent clinical studies have revealed that small size or thinness at birth is associated with increased risk of developing metabolic dysfunctions like obesity, type 2 diabetes, and abnormal lipid and carbohydrate metabolism, leading to coronary heart disease and elevated blood pressure in adulthood (2, 21). This has spurred an increasing interest in the long-term consequences of maternal nutrition during pregnancy and early postnatal nutrition, a phenomenon first described by Hales and Barker (22) and termed metabolic programming. Although this concept is now widely accepted, the mechanisms behind it remain poorly understood. The observed effects reflect phenotypical alterations, probably established through epigenetic mechanisms, which occur as a result of fetal adaptations to intrauterine and probably early postnatal influences (23, 38). Maternal low-protein diet during pregnancy in rats may in adulthood result in reduced glucose tolerance and high blood pressure, evidently due to a prenatally programmed tendency to dysfunction of small arteries and abnormal pancreatic development (9, 17, 25). Likewise, maternal low-protein diets may result in very significantly shortened life span in mice offspring (44). Thus, both the type of malnutrition and the time of exposure during pregnancy appear to influence the programming effects observed later in life (21, 23). Furthermore, the potentially de...

During exhaustive exercise in cirrhotic patients the CMR is maintained and a significant cerebral uptake of lactate is demonstrated. The data suggest that oral treatment with a non-selective beta-adrenergic receptor antagonist attenuates cerebral non-oxidative metabolism.

Obesity is known to increase the risk of labour dystocia and insufficient energy supply, due to reduced mitochondrial capacity or quantity, could be a possible mechanism leading to reduced efficiency of uterine contractility during labour. In the present study of 36 women having an elective Caesarean section at term, obesity did not change mitochondrial phenotype in the myometrial myocyte obtained from uterine biopsies taken at delivery. Respiration rates in isolated mitochondria were unaffected by obesity. No indication of reduced content, investigated by quantification of the complexes of the respiratory chain, or altered regulation, examined by myometrial mRNA levels of genes related to mitochondrial biogenesis and inflammation, was detected. Yet we found increased myometrial triglyceride content in the obese group (2.39 ± 0.26 vs. 1.56 ± 0.20 mm, P = 0.024), while protein content and citrate synthase activity per gram wet weight myometrium were significantly lower in the obese (109.2 ± 7.2 vs. 139.4 ± 5.6 mg g , P = 0.002, and 24.8 ± 1.0 vs. 29.6 ± 1.4 U g wet wt, P = 0.008, respectively). These differences were substantiated by our histological findings where staining for nuclei, cytoplasm, glycogen and collagen supported the idea of a smaller muscle content in the myometrium in obese women. In conclusion no indication of myometrial mitochondrial dysfunction in the isolated state was found, but the observed increase of lipid content might play a role in the pathophysiological mechanisms behind labour dystocia in obese women.