Exercise training alters lipoprotein particles independent of brown adipose tissue metabolic activity

IntroductionNew strategies for weight loss and weight maintenance in humans are needed. Human brown adipose tissue (BAT) can stimulate energy expenditure and may be a potential therapeutic target for obesity and type 2 diabetes. However, whether exercise training is an efficient stimulus to activate and recruit BAT remains to be explored. This study aimed to evaluate whether regular exercise training affects cold‐stimulated BAT metabolism and, if so, whether this was associated with changes in plasma metabolites.MethodsHealthy sedentary men (n = 11; aged 31 [SD 7] years; body mass index 23 [0.9] kg m−2; VO2 max 39 [7.6] mL min−1 kg−1) participated in a 6‐week exercise training intervention. Fasting BAT and neck muscle glucose uptake (GU) were measured using quantitative [18F]fluorodeoxyglucose positron emission tomography–magnetic resonance imaging three times: (1) before training at room temperature and (2) before and (3) after the training period during cold stimulation. Cervico‐thoracic BAT mass was measured using MRI signal fat fraction maps. Plasma metabolites were analysed using nuclear magnetic resonance spectroscopy.ResultsCold exposure increased supraclavicular BAT GU by threefold (p p p p = 0.01) and decreased visceral fat (p = 0.02) and cervico‐thoracic BAT mass (p = 0.003). Additionally, training decreased very low‐density lipoprotein particle size (p = 0.04), triglycerides within chylomicrons (p = 0.04) and small high‐density lipoprotein (p = 0.04).ConclusionsAlthough exercise training plays an important role for metabolic health, its beneficial effects on whole body metabolism through physiological adaptations seem to be independent of BAT activation in young, sedentary men.</div

Exercise Training Modulates Gut Microbiota Profile and Improves Endotoxemia

Introduction: Intestinal metabolism and microbiota profiles are impaired in obesity and insulin resistance. Moreover, dysbiotic gut microbiota has been suggested to promote systemic low-grade inflammation and insulin resistance through the release of endotoxins particularly lipopolysaccharides. We have previously shown that exercise training improves intestinal metabolism in healthy men. To understand whether changes in intestinal metabolism interact with gut microbiota and its release of inflammatory markers, we studied the effects of sprint interval (SIT) and moderate-intensity continuous training (MICT) on intestinal metabolism and microbiota in subjects with insulin resistance. Methods: Twenty-six, sedentary subjects (prediabetic, n = 9; type 2 diabetes, n = 17; age, 49 [SD, 4] yr; body mass index, 30.5 [SD, 3]) were randomized into SIT or MICT. Intestinal insulin-stimulated glucose uptake (GU) and fatty acid uptake (FAU) from circulation were measured using positron emission tomography. Gut microbiota composition was analyzed by 16S rRNA gene sequencing and serum inflammatory markers with multiplex assays and enzyme-linked immunoassay kit. Results: V˙O2peak improved only after SIT (P = 0.01). Both training modes reduced systematic and intestinal inflammatory markers (tumor necrosis factor-α, lipopolysaccharide binding protein) (time P < 0.05). Training modified microbiota profile by increasing Bacteroidetes phylum (time P = 0.03) and decreasing Firmicutes/Bacteroidetes ratio (time P = 0.04). Moreover, there was a decrease in Clostridium genus (time P = 0.04) and Blautia (time P = 0.051). Only MICT decreased jejunal FAU (P = 0.02). Training had no significant effect on intestinal GU. Colonic GU associated positively with Bacteroidetes and inversely with Firmicutes phylum, ratio Firmicutes/Bacteroidetes and Blautia genus. Conclusions: Intestinal substrate uptake associates with gut microbiota composition and whole-body insulin sensitivity. Exercise training improves gut microbiota profiles and reduces endotoxemia.This study was conducted within the Centre of Excellence in Cardiovascular and Metabolic Diseases and supported by the Academy of Finland, the University of Turku, Turku University Hospital, and Åbo Akademi University. The study was financially supported by the European Foundation for the Study of Diabetes, the Finnish Cultural Foundation, Varsinais-Suomi Regional Fund, Juho Vainio Foundation, Emil Aaltonen Foundation, Hospital District of Southwest Finland, Orion Research Foundation, Finnish Diabetes Foundation, Ministry of Education of the State of Finland, Academy of Finland (grants 251399 and 256470), Paavo Nurmi Foundation, Novo Nordisk Foundation and the Centre of Excellence funding.Peer reviewe

Brain substrate metabolism and ß-cell function in humans: A positron emission tomography study.

Aims: Recent clinical studies have shown enhanced brain glucose uptake during clamp and brain fatty acid uptake in insulin-resistant individuals. Preclinical studies suggest that the brain may be involved in the control of insulin secretion. The aim of this study was to investigate whether brain metabolism assessed as brain glucose and fatty acid uptake is associated with the parameters of β-cell function in humans. Materials and methods: We analysed cross-sectional data of 120 subjects across a wide range of BMI and insulin sensitivity. Brain glucose uptake (BGU) was measured during euglycaemic-hyperinsulinaemic clamp (n&nbsp;=&nbsp;67) and/or during fasting (n&nbsp;=&nbsp;45) using [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). In another group of subjects (n&nbsp;=&nbsp;34), brain fatty acid uptake was measured using [18F]-fluoro-6-thia-heptadecanoic acid (FTHA) PET during fasting. The parameters of β-cell function were derived from OGTT modelling. Statistical analysis was performed with whole-brain voxel-based statistical parametric mapping. Results: In non-diabetics, BGU during euglycaemic hyperinsulinaemic&nbsp;clamp correlated positively with basal insulin secretion rate (r&nbsp;=&nbsp;0.51, P&nbsp;=&nbsp;.0008) and total insulin output (r&nbsp;=&nbsp;0.51, P&nbsp;=&nbsp;.0008), whereas no correlation was found in type 2 diabetics. BGU during clamp correlated positively with potentiation in non-diabetics (r&nbsp;=&nbsp;0.33, P&nbsp;=&nbsp;.02) and negatively in type 2 diabetics (r&nbsp;=&nbsp;-0.61, P&nbsp;=&nbsp;.02). The associations in non-diabetics were not explained with whole-body insulin sensitivity or BMI. No correlations were found between baseline (fasting) BGU and basal insulin secretion rate, whereas baseline brain fatty acid uptake correlated directly with basal insulin secretion rate (r&nbsp;=&nbsp;0.39, P&nbsp;=&nbsp;.02) and inversely with potentiation (r&nbsp;=&nbsp;-0.36, P&nbsp;=&nbsp;.04). Conclusions: Our study provides coherent, though correlative, evidence that, in humans, the brain may be involved in the control of insulin secretion independently of insulin sensitivity