Exercise training induces insulin-sensitizing PAHSAs in adipose tissue of elderly women
Graphical abstract
Introduction
Aging is associated with redistribution of adipose tissue (AT), characterized by increased visceral and ectopic fat deposition, which may be independent of changes in body weight due to concomitant decreases in muscle mass (sarcopenia) [1]. These changes are then related to an increased risk of metabolic diseases such as type 2 diabetes and cardiovascular disease [1]. Thus, AT dysfunction appears to be one of the important contributors to impaired metabolic status in the elderly; it is characterized by altered lipid storage, impaired de novo lipogenesis (DNL) and lipolysis, and increased pro-inflammatory state due to changes in innate immunity [2,3]. Circulating pro-inflammatory cytokines secreted by AT have been suggested to promote sarcopenia in the elderly, and obesity was the main factor explaining poorer physical performance in older adults with metabolic syndrome [4].
In the elderly, lifestyle interventions based on the increased physical activity are primarily aimed to improve muscle function and/or cardiovascular fitness, but recent data suggest that AT may also contribute to the beneficial effects of exercise on systemic inflammation and overall health [5]. Accordingly, it has been shown that exercise-induced lipokines increasing muscle fatty acid (FA) uptake are produced in brown AT [6], while transplantation of AT from mice subjected to exercise training (ET) into their sedentary counterparts improved glucose homeostasis of the recipients [5,7]. Moreover, AT was identified as a source of branched FA esters of hydroxy FA (FAHFA), i.e. a growing family of endogenous lipids with documented anti-inflammatory and insulin-sensitizing effects at the systemic level [[8], [9], [10]], whose regulation and relevance to the beneficial effects of exercise are currently unknown.
The pro-inflammatory phenotype may also be affected by natural substances such as omega-3 polyunsaturated fatty acids (PUFA) and specialized pro-resolving mediators [[11], [12], [13]]. Omega-3 PUFA supplementation reduced AT and systemic inflammation in obese non-diabetic subjects [13], and it could represent a potential strategy for the treatment/prevention of sarcopenia through increased muscle protein synthesis [14]. Calanus oil represents a novel source of omega-3 PUFA, which is unique in its combination of PUFA and alcohols [15]. Moreover, in dietary obese mice, supplementation of omega-3 PUFA-containing wax esters from Calanus oil ameliorated AT dysfunction more effectively than the same dose of omega-3 PUFA administered as ethyl esters [16,17].
Thus, the objective of this study was to evaluate in older sedentary individuals the effect of ET alone, or in combination with Calanus oil, on serum and AT lipidome and its relationship to insulin sensitivity as well as other clinical parameters.
Section snippets
Study design
This work is based on the clinical study EXODYA (Effect of Exercise training and Omega-3 fatty acids on metabolic health and Dysfunction of Adipose tissue in elderly; NCT number: NCT03386461), and focuses primarily on the presentation of lipidomics data and their association with clinical parameters. Briefly, fifty-five healthy sedentary women aged 65–80 were enrolled in the physical activity program (i.e. ET) that consisted of supervised combined aerobic (mainly nordic walking, moderate
Exercise improved physical fitness and insulin sensitivity
We aimed to reveal whether ET, alone or combined with omega-3 PUFA supplementation, could affect adiposity and whole-body parameters of physical fitness and glucose metabolism. Although we did not observe significant changes in body weight, BMI, fat mass and fat free mass in response to either ET or ET with omega-3 PUFA, physical fitness was improved by ET regardless of omega-3 PUFA supplementation, as indicated by changes in VO2 max (Table 1). Moreover, whole body insulin sensitivity,
Discussion
The aim of this part of the EXODYA project was to analyze the effects of ET on serum and AT metabolome and lipidome in elderly women, and to explore potential synergy between ET and omega-3 PUFA supplementation in these effects. The analysis of anthropometric and biochemical parameters showed a beneficial effect of ET on whole-body fitness, but failed to prove an additive effect of a low dose of omega-3 PUFA. There could be several reasons for this finding. The form of omega-3 PUFA used in this
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Acknowledgments
This work was supported by grants from the Ministry of Health of the Czech Republic 16-29182A, Czech Science Foundation 17-10088Y, Czech Ministry of Education, Youth and Sports LTAUSA17173 and the Czech Academy of Sciences (Lumina quaeruntur 2018). Sunflower oil and Calanus oil capsules were provided by Calanus AS, Norway. NCT number: NCT03386461.
Declaration of competing interests
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Author contributions
Conceptualization: K.D., M.Si., M.R. and O.K.; Data curation: M.B., T.C., M.O., M.S., K.D., L.R., M.M., M.Si. and O.K.; Formal analysis: M.B., T.C., M.O., M.S., K.D., L.R., M.M., M.Si. and O.K.; Funding acquisition: K.D., M.Si., M.R. and O.K.; Investigation: M.B., T.C., M.O., M.S., K.D., L.R., M.M., M.Si. and O.K.; Methodology: T.C., K.D., M.M., M.Si. and O.K.; Project administration: M.Si. and M.R.; Resources: M.Si. and O.K.; Software: T.C.; Supervision: M.Si. and O.K.; Validation: M.R.;
References (40)
- et al.
Adipose tissue, diet and aging
Mech. Ageing Dev.
(2014) - et al.
Adipose tissue inflammation in aging
Exp. Gerontol.
(2018) - et al.
Aging and adipose tissue: potential interventions for diabetes and regenerative medicine
Exp. Gerontol.
(2016) - et al.
Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects
Cell
(2014) - et al.
Omega-3 fatty acids and adipose tissue biology
Mol. Asp. Med.
(2018) - et al.
Long-chain n-3 PUFAs reduce adipose tissue and systemic inflammation in severely obese nondiabetic patients: a randomized controlled trial
Am. J. Clin. Nutr.
(2012) - et al.
Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: a randomized controlled trial
Am. J. Clin. Nutr.
(2011) - et al.
Wax esters from the marine copepod Calanus finmarchicus reduce diet-induced obesity and obesity-related metabolic disorders in mice
J. Nutr.
(2014) On the complexity of PAHSA research
Cell Metab.
(2018)- et al.
Omega-3 index in the Czech Republic: no difference between urban and rural populations
Chem. Phys. Lipids
(2019)
Methodological issues in studying PAHSA biology: masking PAHSA effects
Cell Metab.
Differences in the regulation of adipose tissue and liver lipogenesis by carbohydrates in humans
J. Lipid Res.
Omega-3 supplementation with resistance training does not improve body composition or lower biomarkers of inflammation more so than resistance training alone in older men
Nutr. Res.
Selective partitioning of dietary fatty acids into the VLDL TG pool in the early postprandial period
J. Lipid Res.
Levels of palmitic acid ester of hydroxystearic acid (PAHSA) are reduced in the breast milk of obese mothers
BBA
The role of metabolic syndrome, adiposity, and inflammation in physical performance in the Health ABC study
J. Gerontol. A Biol. Sci. Med. Sci.
Exercise regulation of adipose tissue
Adipocyte
12,13-diHOME: an exercise-induced lipokine that increases skeletal muscle fatty acid uptake
Cell Metab.
A novel role for subcutaneous adipose tissue in exercise-induced improvements in glucose homeostasis
Diabetes
Docosahexaenoic acid-derived fatty acid esters of hydroxy fatty acids (FAHFAs) with anti-inflammatory properties
Diabetes
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