Exercise-Induced Changes in Visceral Adipose Tissue Mass are Regulated by IL-6 Signaling: A Randomized Controlled Trial

Wedell‐Neergaard, Anne‐Sophie; Lehrskov, Louise Lang; Christensen, Regitse Højgaard; Legaard, Grit Elster; Dorph, Emma; Larsen, Monica Korsager; Launbo, Natja; Fagerlind, Sabrina Ravn; Seide, Sidsel Kofoed; Nymand, Stine; Ball, Maria; Vinum, Nicole; Dahl, Camilla Noerfelt; Ried‐Larsen, Mathias; Nybing, Janus Damm; Christensen, R.; Rosenmeyer, Jaya Birgitte; Karstoft, Kristian; Pedersen, Bente Klarlund; Ellingsgaard, Helga; Krogh-Madsen, Rikke

doi:10.2139/ssrn.3254906

Cited by 54 publications

(80 citation statements)

References 39 publications

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“…This suggests that NOX2 regulates exercise-stimulated IL-6 expression in skeletal muscle, possibly via NF-jB signaling (Fig. 8), which could be related to IL-6-mediated exercise benefits recently published in humans (199,372). Studies testing the role of NOX2 directly in IL-6-mediated benefits after exercise training are highly required.…”

Section: Nox2 and Exercise-stimulated Myokinesmentioning

confidence: 91%

The Emerging Roles of Nicotinamide Adenine Dinucleotide Phosphate Oxidase 2 in Skeletal Muscle Redox Signaling and Metabolism

Henríquez‐Olguín

Boronat

Cabello-Verrugio

et al. 2019

Antioxidants & Redox Signaling

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Significance: Skeletal muscle is a crucial tissue to whole-body locomotion and metabolic health. Reactive oxygen species (ROS) have emerged as intracellular messengers participating in both physiological and pathological adaptations in skeletal muscle. A complex interplay between ROS-producing enzymes and antioxidant networks exists in different subcellular compartments of mature skeletal muscle. Recent evidence suggests that nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) are a major source of contraction-and insulin-stimulated oxidants production, but they may paradoxically also contribute to muscle insulin resistance and atrophy. Recent Advances: Pharmacological and molecular biological tools, including redox-sensitive probes and transgenic mouse models, have generated novel insights into compartmentalized redox signaling and suggested that NOX2 contributes to redox control of skeletal muscle metabolism. Critical Issues: Major outstanding questions in skeletal muscle include where NOX2 activation occurs under different conditions in health and disease, how NOX2 activation is regulated, how superoxide/hydrogen peroxide generated by NOX2 reaches the cytosol, what the signaling mediators are downstream of NOX2, and the role of NOX2 for different physiological and pathophysiological processes. Future Directions: Future research should utilize and expand the current redox-signaling toolbox to clarify the NOX2-dependent mechanisms in skeletal muscle and determine whether the proposed functions of NOX2 in cells and animal models are conserved into humans.

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Section: Nox2 and Exercise-stimulated Myokinesmentioning

confidence: 91%

The Emerging Roles of Nicotinamide Adenine Dinucleotide Phosphate Oxidase 2 in Skeletal Muscle Redox Signaling and Metabolism

Henríquez‐Olguín

Boronat

Cabello-Verrugio

et al. 2019

Antioxidants & Redox Signaling

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“…To gain some insight into this biological complexity, we examined an alternative physiological mechanism that promotes IL6 signaling in adipose tissue. For example, it is established that IL6 secreted by skeletal muscle after exercise targets adipose tissue (11). We therefore compared adipose tissue in control M WT mice (Mck-Cre +/− ) and M ΔIL6 mice Fig.…”

Section: Il6 Signaling Differentially Regulates Adipose Tissue Inflammentioning

confidence: 99%

“…Moreover, IL6 acts on adipose tissue to increase leptin secretion and suppress satiety (8), and IL6 increases adipose tissue lipolysis (8), which, in turn, promotes hepatic gluconeogenesis (9) and hepatic insulin resistance (9,10). IL6 also increases the loss of adipose tissue following exercise (11) and in response to cancer cachexia (12). Furthermore, IL6 signaling in the paraventricular nucleus of the hypothalamus improves energy and glucose homeostasis in response to obesity (13).…”

mentioning

confidence: 99%

Regulation of adipose tissue inflammation by interleukin 6

Han

White

Perry

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

244

194

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Obesity is associated with a chronic state of low-grade inflammation and progressive tissue infiltration by immune cells and increased expression of inflammatory cytokines. It is established that interleukin 6 (IL6) regulates multiple aspects of metabolism, including glucose disposal, lipolysis, oxidative metabolism, and energy expenditure. IL6 is secreted by many tissues, but the role of individual cell types is unclear. We tested the role of specific cells using a mouse model with conditional expression of the Il6 gene. We found that IL6 derived from adipocytes increased, while IL6 derived from myeloid cells and muscle suppressed, macrophage infiltration of adipose tissue. These opposite actions were associated with a switch of IL6 signaling from a canonical mode (myeloid cells) to a noncanonical trans-signaling mode (adipocytes and muscle) with increased expression of the ADAM10/17 metalloprotease that promotes trans-signaling by the soluble IL6 receptor α. Collectively, these data demonstrate that the source of IL6 production plays a major role in the physiological regulation of metabolism.

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“…The mechanisms through which physical activity/exercise reduces IHTAG content have received relatively little attention. A recent hypothesis relates to the myokine interleukin-6 (IL-6) which is increased in response to exercise [72]; it is suggested that IL-6 signalling mediates exercise-induced reductions in visceral adipose tissue mass [73]. IL-6 treatment in rat hepatocytes led to increased secretion of apolipoprotein B (ApoB)-containing lipoproteins [74] and an increased secretion of TAG-rich lipoproteins may play a role in the reduction of IHTAG content [75].…”

Section: Proposed Molecular Mechanisms Underpinning Lifestyle Intervementioning

confidence: 99%

Managing NAFLD in Type 2 Diabetes: The Effect of Lifestyle Interventions, a Narrative Review

Parry

Hodson

2020

Adv Ther

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The prevalence of non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) is increasing. As a strong association between these two diseases exist, it is unsurprising that the number of patients with coexisting NAFLD and T2D is also increasing. These patients display a deleterious metabolic profile (e.g. hypertriglyceridemia), and increased mortality rates relative to those with only NAFLD or T2D in isolation; therefore, effective treatment strategies are required. Here we review the available intervention studies that have investigated the effects of changes in lifestyle (diet and exercise/physical activity) on NAFLD in patients with both NAFLD and T2D. On the basis of the available evidence, it appears that the addition of any kind of exercise (i.e. resistance, aerobic, or high-intensity intermittent exercise) is beneficial for patients with both NAFLD and T2D. These effects appear to occur independently of changes in body weight. Hypocaloric diets leading to weight loss are also effective in improving metabolic parameters in patients with both NAFLD and T2D, with data indicating that * 7-10% weight loss is required in order to observe beneficial effects. It is unclear if multidisciplinary interventions incorporating changes in both diet and physical activity levels are a more effective treatment strategy in this population than diet or exercise interventions in isolation. In conclusion, it is clear that lifestyle interventions are an effective treatment strategy in patients with both NAFLD and T2D, although further research is required to optimise these interventions and determine their scalability.

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Exercise-Induced Changes in Visceral Adipose Tissue Mass are Regulated by IL-6 Signaling: A Randomized Controlled Trial

Cited by 54 publications

References 39 publications

The Emerging Roles of Nicotinamide Adenine Dinucleotide Phosphate Oxidase 2 in Skeletal Muscle Redox Signaling and Metabolism

The Emerging Roles of Nicotinamide Adenine Dinucleotide Phosphate Oxidase 2 in Skeletal Muscle Redox Signaling and Metabolism

Regulation of adipose tissue inflammation by interleukin 6

Managing NAFLD in Type 2 Diabetes: The Effect of Lifestyle Interventions, a Narrative Review

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