bims-exemet 2021-09-05 papers

Issue of 2021–09–05
four papers selected by
Javier Botella Ruiz, Victoria University

Diabetes Obes Metab. 2021 Sep 02.

A single bout of cycling exercise induces nucleosome repositioning in skeletal muscle of lean and obese individuals.

Prasad P Devarshi, Andrea S Pereyra, Jessica M Ellis, Tara M Henagan.

Acute aerobic exercise improves, whereas being overweight impairs, skeletal muscle mitochondrial function in correlation with reduced insulin sensitivity. Here, the molecular and metabolic effects of a single exercise bout in the skeletal muscle was compared in men, aged 19-30 years, that were either lean (BMI<25, 18.5-24.1 kg/m2 , n=15) or overweight/obese (Ov/Ob; BMI≥25, 25.5-36.9 kg/m2 , n=15). Four hours after a high-carbohydrate breakfast (7 kcal/kg; 60% carbohydrate, 25% fat, 15% protein), participants performed cycling exercise (50% VO2 max, expending ~650 kcal). Muscle biopsies and peripheral blood samples were collected 30 minutes before the meal and immediately after exercise. Muscle long-chain acylcarnitines were increased in Ov/Ob compared to lean, with or without exercise. A single exercise bout increased mRNA abundance of genes related to mitochondria and insulin signaling in both lean and Ov/Ob. Nucleosome mapping by micrococcal nuclease digestion with deep sequencing (MNase-seq) revealed that exercise repositioned the -1N nucleosome away from the transcription start site of the PGC1a promoter and of other mitochondrial genes, but did not affect genes related to insulin signaling, in both lean and Ov/Ob. In conclusion, these data suggest that a single exercise bout induced epigenetic alterations in skeletal muscle in a BMI-independent manner. This article is protected by copyright. All rights reserved.

DOI: https://doi.org/10.1111/dom.14541

Front Physiol. 2021 ;12 709807

The Role of the Skeletal Muscle Secretome in Mediating Endurance and Resistance Training Adaptations.

Aurel B Leuchtmann, Volkan Adak, Sedat Dilbaz, Christoph Handschin.

Exercise, in the form of endurance or resistance training, leads to specific molecular and cellular adaptions not only in skeletal muscles, but also in many other organs such as the brain, liver, fat or bone. In addition to direct effects of exercise on these organs, the production and release of a plethora of different signaling molecules from skeletal muscle are a centerpiece of systemic plasticity. Most studies have so far focused on the regulation and function of such myokines in acute exercise bouts. In contrast, the secretome of long-term training adaptation remains less well understood, and the contribution of non-myokine factors, including metabolites, enzymes, microRNAs or mitochondrial DNA transported in extracellular vesicles or by other means, is underappreciated. In this review, we therefore provide an overview on the current knowledge of endurance and resistance exercise-induced factors of the skeletal muscle secretome that mediate muscular and systemic adaptations to long-term training. Targeting these factors and leveraging their functions could not only have broad implications for athletic performance, but also for the prevention and therapy in diseased and elderly populations.

Keywords: PGC-1alpha; endurance training; exercise; myokines; resistance training; secretome; skeletal muscle

DOI: https://doi.org/10.3389/fphys.2021.709807

Obesity (Silver Spring). 2021 Aug 31.

Eight-week exercise training in humans with obesity: Marked improvements in insulin sensitivity and modest changes in gut microbiome.

Rebecca J H M Verheggen, Prokopis Konstanti, Hauke Smidt, Ad R M M Hermus, Dick H J Thijssen, Maria T E Hopman.

OBJECTIVE: Obesity is associated with impaired gut microbiota diversity, which has been linked to the development of type 2 diabetes. This study aims to examine the effects of an 8-week aerobic exercise intervention on insulin sensitivity, visceral adiposity, and gut microbiota diversity and composition in participants with obesity.
METHODS: Fourteen participants (mean [SD], age 51 [11] years; BMI 34.9 [4.9] kg/m2 ) performed an 8-week exercise intervention (2 to 4 times/week on 65% to 85% of heart rate reserve). Insulin sensitivity (hyperinsulemic euglycemic clamp), cardiorespiratory fitness (maximal oxygen uptake), visceral adiposity (dual-energy X-ray absorptiometry scan) and gut microbiota composition (16S rRNA gene sequencing) were measured before and after the intervention.
RESULTS: Insulin sensitivity showed a significant increase (pre: 3.8 [1.9] mg/min/kg; post: 4.5 [1.7] mg/min/kg; p = 0.007) after training, whereas visceral adiposity decreased (pre: 959 [361] cm3 ; post: 897 [364] cm3 ; p = 0.02). No change in gut microbiota α- or β-diversity was found. At the genus level, the abundance of Ruminococcus gauvreauii (p = 0.02); Lachnospiraceae FCS020 group (p = 0.04), and Anaerostipes (p = 0.04) significantly increased after exercise training. Significant positive correlations were present for M-value (R. gauvreauii) and VO2 max (R. gauvreauii and Anaerostipes).
CONCLUSIONS: Eight-week exercise training in humans with obesity leads to marked improvements in insulin sensitivity and body composition and is accompanied by modest changes in 3 gut microbiome genera, all belonging to the Firmicutes phylum.

DOI: https://doi.org/10.1002/oby.23252

Metabolism. 2021 Aug 31. pii: S0026-0495(21)00173-6. [Epub ahead of print] 154873

Diet and exercise reduce pre-existing NASH and fibrosis and have additional beneficial effects on the vasculature, adipose tissue and skeletal muscle via organ-crosstalk.

Anita M van den Hoek, Jelle C B C de Jong, Nicole Worms, Anita van Nieuwkoop, Marijke Voskuilen, Aswin L Menke, Serene Lek, Martien P M Caspers, Lars Verschuren, Robert Kleemann.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) has become one of the most common liver diseases and is still without approved pharmacotherapy. Lifestyle interventions using exercise and diet change remain the current treatment of choice and even a small weight loss (5-7%) can already have a beneficial effect on NASH. However, the underlying molecular mechanisms of exercise and diet interventions remain largely elusive, and it is unclear whether they exert their health effects via similar or different pathways.
METHODS: Ldlr-/-.Leiden mice received a high fat diet (HFD) for 30 weeks to establish a severe state of NASH/fibrosis with simultaneous atherosclerosis development. Groups of mice were then either left untreated (control group) or were treated for 20 weeks with exercise (running wheel), diet change (switch to a low fat chow diet) or the combination thereof. The liver and distant organs including heart, white adipose tissue (WAT) and muscle were histologically examined. Comprehensive transcriptome analysis of liver, WAT and muscle revealed the organ-specific effects of exercise and diet and defined the underlying pathways.
RESULTS: Exercise and dietary change significantly reduced body weight, fat mass, adipocyte size and improved myosteatosis and muscle function with additive effects of combination treatment. WAT inflammation was significantly improved by diet change, tended to be reduced with exercise, and combination therapy had no additive effect. Hepatic steatosis and inflammation were almost fully reversed by exercise and diet change, while hepatic fibrosis tended to be improved with exercise and was significantly improved with diet change. Additive effects for the combination therapy were shown for liver steatosis and associated liver lipids, and atherosclerosis, but not for hepatic inflammation and fibrosis. Pathway analysis revealed complementary effects on metabolic pathways and lipid handling processes, thereby substantiating the added value of combined lifestyle treatment.
CONCLUSIONS: Exercise, diet change and the combination thereof can reverse established NASH/fibrosis in obese Ldlr-/-.Leiden mice. In addition, the lifestyle interventions had beneficial effects on atherosclerosis, WAT inflammation and muscle function. For steatosis and other parameters related to adiposity or lipid metabolism, exercise and dietary change affected more distinct pathways that acted complementary when the interventions were combined resulting in an additive effect for the combination therapy on important endpoints including NASH and atherosclerosis. For inflammation, exercise and diet change shared several underlying pathways resulting in a net similar effect when the interventions were combined.

Keywords: Atherosclerosis; Fibrosis; Lifestyle interventions; Muscle-liver axis; NAFLD; WAT-liver axis

DOI: https://doi.org/10.1016/j.metabol.2021.154873