An exercise intervention without weight loss decreases circulating interleukin-6 in lean and obese men with and without type 2 diabetes mellitus
Introduction
Chronic low-grade inflammation, characterized by abnormal production of adipokines and inflammatory mediators, has been implicated in the pathogenesis of obesity-related chronic diseases including what may be called the obesity–type 2 diabetes mellitus (T2DM)–cardiovascular disease (CVD) triad [1], [2]. In particular, novel CVD biomarkers such as interleukin-6 (IL-6) [3], [4], the acute-phase reactant C-reactive protein (CRP), [5], [6] and the antifibrinolytic plasminogen activator inhibitor 1 (PAI-1) [7], [8] are elevated in obesity and have all been associated with insulin resistance, a hallmark of the obesity-diabetes-CVD triad. Increased visceral adipose tissue is also associated with insulin resistance observed in obese men [9], [10].
The role of lifestyle intervention in lowering the risk of CVD has been well studied. Lifestyle modifications that include exercise-induced weight loss have been associated with decreases in IL-6, CRP, and PAI-1 concentrations [11], [12], [13]. The actual impact of an exercise intervention alone on circulating cytokine concentrations is difficult to evaluate in such studies with an exercise program designed to induce body weight loss. However, other studies have shown that an exercise intervention without weight loss may be an effective strategy to promote favorable metabolic changes in abdominal obesity and waist circumference in obese individuals with and without T2DM [14]. It is unclear whether exercise-induced improvements in adiposity and waist circumference in the absence of weight loss may have an impact on circulating inflammatory biomarkers implicated in the obesity-diabetes-CVD triad.
The purpose of this study was to evaluate blood concentrations of 3 CVD biomarkers—IL-6, CRP, and PAI-1—before and after a 12-week exercise intervention without weight loss in previously sedentary lean men and obese men with and without T2DM. Insulin sensitivity and body composition were also assessed before and after the exercise intervention, and the results have been previously reported [15].
Section snippets
Subjects
Twenty-four men (8 lean, 8 obese, 8 obese with T2DM) were recruited from Kingston, Ontario, through the general media. All subjects were white nonsmokers who consumed, on average, less than 2 alcoholic drinks per day and led a sedentary lifestyle (no participation in any regular physical activity for the past 6 months). Before inclusion in the study, obese men underwent an oral glucose tolerance test to screen for T2DM. Subjects with T2DM were not taking insulin or insulin sensitizers and were
Baseline subject characteristics
Physical and clinical characteristics for the subjects pre- and post-intervention were previously published [15] and have been summarized in Table 1 for completeness of data. As expected, before the exercise intervention (PRE), subjects in the obese and T2DM groups had higher (P < .05) body weight, body mass index (BMI), total and visceral adiposity, and waist circumference compared with the lean group (Table 1). Mean energy expenditure was not different among the groups at weeks 1, 4, 8, and
Discussion
A 12-week exercise intervention without weight loss resulted in a significant change in the phenotype of obesity. Our study is the first to report a significant decrease in circulating IL-6, alongside a decrease in visceral adipose tissue and waist circumference, in lean subjects, obese subjects, and subjects with T2DM who underwent an exercise program without weight loss. Although no statistically significant correlations were found with our relatively small sample size, it is conceivable that
Acknowledgments
This research was supported by a Natural Sciences and Engineering Research Council Collaborative Health Research Grant (TEG) and a Natural Sciences and Engineering Research Council Discovery Grant (LER). Mark J. Dekker is supported by the Heart and Stroke Foundation of Ontario Master's Studentship.
The authors thank the study participants and Lance Davidson, Diana Hall, Jennifer Kuk, Ann-Marie Kungl, Meghan Watts, Suzy Wong, Premila Sathasivam, Anila Mathai, and Jennifer Shinde for their
References (37)
- et al.
Low-grade inflammation may play a role in the etiology of the metabolic syndrome in patients with coronary heart disease: the HIFMECH study
Metabolism
(2004) - et al.
Waist circumference and not body mass index explains obesity-related health risk
Am J Clin Nutr
(2004) - et al.
Interleukin 6, adiponectin, leptin, and insulin resistance in nonobese Japanese type 2 diabetic patients
Metabolism
(2006) - et al.
Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-α and IL-6
Diabetes Res Clin Pract
(2005) - et al.
Exercise training is not associated with improved levels of C-reactive protein or adiponectin
Metabolism
(2005) - et al.
The decrease in C-reactive protein concentration after diet and physical activity induced weight reduction is associated with changes in plasma lipids, but not interleukin-6 or adiponectin
Metabolism
(2006) - et al.
Tumor necrosis factor (TNF) inhibits interleukin (IL)–1 and/or IL-6 stimulated synthesis of C-reactive protein (CRP) and serum amyloid A (SAA) in primary cultures of human hepatocytes
Biochim Biophys Acta
(1991) - et al.
C-reactive protein, interleukin-6 and tumor necrosis factor α as predictors of incident coronary and cardiovascular events and total mortality. A population-based, prospective study
Thromb Haemost
(2006) - et al.
Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro
J Clin Endocrinol Metab
(2002) - et al.
NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X
Diabetologia
(1997)
Low insulin sensitivity (S(i) = 0) in diabetic and nondiabetic subjects in the insulin resistance atherosclerosis study: is it associated with components of the metabolic syndrome and nontraditional risk factors?
Diabetes Care
Differentiation between obesity and insulin resistance in the association with C-reactive protein
Circulation
Relationship between plasma plasminogen activator inhibitor 1 and insulin resistance
Diabetes Metab Res Rev
Plasminogen activator inhibitor–1 and haemostasis in obesity
Proc Nutr Soc
Abdominal adiposity and insulin resistance in obese men
Am J Physiol Endocrinol Metab
Abdominal fat distribution and peripheral and hepatic insulin resistance in type 2 diabetes mellitus
Am J Physiol Endocrinol Metab
Reductions in plasma cytokine levels with weight loss improve insulin sensitivity in overweight and obese postmenopausal women
Diabetes Care
Lifestyle modification improves endothelial function in obese subjects with the insulin resistance syndrome
Diabetes Care
Cited by (144)
The effects of stress on cardiovascular disease and Alzheimer's disease: Physical exercise as a counteract measure
2020, International Review of NeurobiologyPotential exerkines for physical exercise-elicited pro-cognitive effects: Insight from clinical and animal research
2019, International Review of NeurobiologyCitation Excerpt :Two meta-analyses have shown elevated IL-6 levels in patients with major depressive disorder (Dowlati et al., 2010; Haapakoski, Mathieu, Ebmeier, Alenius, & Kivimaki, 2015). Multiple studies adopting different exercise regimens have consistently reported that physical exercise is effective in lowering circulatory IL-6 in obese and diabetic subjects (Dekker et al., 2007; Steensberg et al., 2000) and those with impaired glucose tolerance (Oberbach et al., 2008). Considerably, Lavebratt et al. (2017) have reported that 12 weeks of exercise could significantly reduce depressive symptoms.
Chronic cannabis use is associated with altered monocyte phenotype, immune response, and depression in physically active individuals
2023, Canadian Journal of Physiology and Pharmacology