Measures of substrate oxidation have traditionally been calculated from indirect calorimetry measurements using stoichiometric equations. Although this has proven to be a solid technique and it has become one of the standard techniques to measure whole body substrate metabolism, there are also several limitations that have to be considered. When indirect calorimetry is used during exercise most of the assumptions on which the method is based hold true although changes in the size of the bicarbonate pool at higher exercise intensities may invalidate the calculations of carbohydrate and fat oxidation. Most of the existing equations are based on stoichiometric equations of glucose oxidation and the oxidation of a triacylglycerol that is representative of human adipose tissue. However, in many exercise conditions, glycogen and not glucose is the predominant carbohydrate substrate. Therefore we propose slightly modified equations for the calculation of carbohydrate and fat oxidation for use during low to high intensity exercise. Studies that investigated fat oxidation over a wide range of intensities and that determined the exercise intensity at which fat oxidation is maximal have provided useful insights in the variation in fat oxidation between individuals and in the factors that affect fat oxidation. Fat oxidation during exercise can be influenced by exercise intensity and duration, diet, exercise training, exercise mode and gender. Although a number of important factors regulating fat oxidation have been identified, it is apparent that a considerable degree of inter-subject variability in substrate utilization persists and cannot be explained by the aforementioned factors. Future research should investigate the causes of the large inter-individual differences in fat metabolism between individuals and their links with various disease states.

Highlights d NR supplementation in aged subjects augments the skeletal muscle NAD + metabolome d NR supplementation does not affect skeletal muscle mitochondrial bioenergetics d NR supplementation reduces levels of circulating inflammatory cytokines

This is the first study to show that protein ingested immediately before sleep is effectively digested and absorbed, thereby stimulating muscle protein synthesis and improving whole-body protein balance during postexercise overnight recovery.

ObjectiveTo investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses.DesignTwelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period.ResultsBoth IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose.ConclusionThese data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation.

Pingitore, A. et al. (2017) The diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro. Diabetes, Obesity and Metabolism, 19(2), pp. 257-265. (doi:10.1111/dom.12811) This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/130703/ Accepted ArticleThe diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro. This article is protected by copyright. All rights reserved.This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. propionate on β-cell function in humans and the direct effects of propionate on isolated human islets in vitro. Materials and Methods:For 24 weeks human subjects ingested an inulinpropionate ester that delivers propionate to the colon. Acute insulin, GLP-1 and nonesterified fatty acid (NEFA) levels were quantified pre-and post-supplementation in response to a mixed meal test. Expression of the SCFA receptor FFAR2 in human islets was determined by western blotting and immunohistochemistry. Dynamic insulin secretion from perifused human islets was quantified by radioimmunoassay and islet apoptosis was determined by quantification of caspase 3/7 activities.Results: Colonic propionate delivery in vivo was associated with improved β-cell function with increased insulin secretion that was independent of changes in GLP-1 levels. Human islet β-cells expressed FFAR2 and propionate potentiated dynamic glucose-stimulated insulin secretion in vitro, an effect that was dependent on signalling via protein kinase C. Propionate also protected human islets from apoptosis induced by the NEFA sodium palmitate and inflammatory cytokines. Conclusions:Our results indicate that propionate has beneficial effects on β-cell function in vivo, and in vitro analyses demonstrated that it has direct effects to potentiate glucose-stimulated insulin release and maintain β-cell mass through