An exercise intervention without weight loss decreases circulating interleukin-6 in lean and obese men with and without type 2 diabetes mellitus

doi:10.1016/j.metabol.2006.10.015

Metabolism

Volume 56, Issue 3, March 2007, Pages 332-338

https://doi.org/10.1016/j.metabol.2006.10.015 Get rights and content

Abstract

Obesity and type 2 diabetes mellitus (T2DM) have been associated with a state of chronic low-grade inflammation. We examined the effect of exercise without weight loss on circulating inflammatory biomarkers in previously sedentary lean men and obese men with and without T2DM. Middle-aged men (8 lean, 8 obese, and 8 obese with T2DM) performed 60 minutes of aerobic exercise 5 times per week for 12 weeks without a reduction in body weight. Subjects underwent a hyperinsulinemic-euglycemic clamp before and after the 12-week exercise program to assess insulin sensitivity. Circulating interleukin-6 (IL-6), plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein concentrations were measured by sandwich enzyme-linked immunosorbent assay before and after the exercise intervention. Body fat was measured using magnetic resonance imaging, and waist circumference was recorded for each subject pre- and postexercise intervention. Waist circumference and plasma IL-6 concentrations were significantly lower (P < .05) after exercise training despite no change in body weight or insulin sensitivity. There were no correlations between insulin sensitivity and IL-6. Fasting plasma PAI-1 concentration was significantly lower in the lean group compared with the obese group both pre- and postexercise intervention (P < .05). There were no changes in C-reactive protein or PAI-1 concentrations after exercise training. A 12-week exercise intervention led to reductions in waist circumference and fasting IL-6 concentrations in previously sedentary lean and obese men with or without T2DM, demonstrating significant changes in clinically relevant diabetes-related parameters despite no change in body weight.

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)

J.S. Yudkin 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)
I. Janssen et al.
Waist circumference and not body mass index explains obesity-related health risk
Am J Clin Nutr
(2004)
A. Taniguchi et al.
Interleukin 6, adiponectin, leptin, and insulin resistance in nonobese Japanese type 2 diabetic patients
Metabolism
(2006)
H.S. Park et al.
Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-α and IL-6
Diabetes Res Clin Pract
(2005)
T.J. Marcell et al.
Exercise training is not associated with improved levels of C-reactive protein or adiponectin
Metabolism
(2005)
A. Dvorakova-Lorenzova 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)
S.H. Yap 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)
K. Tuomisto 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)
J.P. Bastard 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)
J.C. Pickup 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)

S.M. Haffner et al.

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

(2003)

T. McLaughlin et al.

Differentiation between obesity and insulin resistance in the association with C-reactive protein

Circulation

(2002)

J.P. Bastard et al.

Relationship between plasma plasminogen activator inhibitor 1 and insulin resistance

Diabetes Metab Res Rev

(2000)

N.J. Mutch et al.

Plasminogen activator inhibitor–1 and haemostasis in obesity

Proc Nutr Soc

(2001)

R. Ross et al.

Abdominal adiposity and insulin resistance in obese men

Am J Physiol Endocrinol Metab

(2002)

Y. Miyazaki et al.

Abdominal fat distribution and peripheral and hepatic insulin resistance in type 2 diabetes mellitus

Am J Physiol Endocrinol Metab

(2002)

A.S. Ryan et al.

Reductions in plasma cytokine levels with weight loss improve insulin sensitivity in overweight and obese postmenopausal women

Diabetes Care

(2004)

O. Hamdy et al.

Lifestyle modification improves endothelial function in obese subjects with the insulin resistance syndrome

Diabetes Care

(2003)

Cited by (144)

The effects of stress on cardiovascular disease and Alzheimer's disease: Physical exercise as a counteract measure
2020, International Review of Neurobiology
AD is a complicated multi-systemic neurological disorder that involves different biological pathways. Several risk factors have been identified, including chronic stress. Chronic stress produces an alteration in the activity of the hypothalamic pituitary adrenal (HPA) system, and the autonomic nervous system (ANS), which over time increase the risk of AD and also the incidence of cardiovascular disease (CVD) and risk factors, such as hypertension, obesity and type 2 diabetes, associated with cognitive impairment and AD. Considering the multi-factorial etiology of AD, understanding the complex interrelationships between different risk factors is of potential interest for designing adequate strategies for preventing, delaying the onset or slowing down the progression of this devastating disease. Thus, in this review we will explore the general mechanisms and evidence linking stress, cardiovascular disease and AD, and discuss the potential benefits of physical activity for AD by counteracting the negative effects of chronic stress, CVD and risk factors.
Potential exerkines for physical exercise-elicited pro-cognitive effects: Insight from clinical and animal research
2019, International Review of Neurobiology
Citation 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.
A sedentary lifestyle is now known as a critical risk factor for accelerated aging-related neurodegenerative disorders. In contract, having regular physical exercise has opposite effects. Clinical findings have suggested that physical exercise can promote brain plasticity, particularly the hippocampus and the prefrontal cortex, that are important for learning and memory and mood regulations. However, the underlying mechanisms are still unclear. Animal studies reveal that the effects of physical exercise on promoting neuroplasticity could be mediated by different exerkines derived from the peripheral system and the brain itself. This book chapter summarizes the recent evidence from clinical and pre-clinical studies showing the emerging mediators for exercise-promoted brain health, including myokines secreted from skeletal muscles, adipokines from adipose tissues, and other factors secreted from the bone and liver.
The relationship between selected body fatness indices and the level of blood interleukin-6 in female nursing home residents aged 80+ years without inflammation: A pilot study
2018, Experimental Gerontology
Interleukin-6 (IL-6) production facilitates a shift from acute to chronic inflammation that may induce the development of some diseases and aging. Several studies have suggested that adiposity is closely related to serum IL-6 level, but their authors examined relatively young older adults (aged 60–80 years), so it is not clear whether this association would also occur in people at a more advanced age.
to assess whether in elderly women without inflammation the widely used anthropometric obesity indices are associated with serum IL-6 level and, if so, to determine the best anthropometric predictor of this inflammatory biomarker.
The sample consisted of 12 women (85.1 ± 3.9 years; 58.1 ± 8.7 kg; 151.9 ± 6.3 cm), the residents of nursing homes, who did not use anti-inflammatory drugs, statins or diuretics and whose blood C-reactive protein (CRP) concentration was lower than 3 mg/l. To determine CRP and IL-6 concentrations, venous blood samples were collected in the morning in a fasted state. The following anthropometric measurements were made in all participants: body weight, body height, the circumferences of waist, hip and neck. Body fat percentage and visceral fat rating (VFR) were determined by bioelectrical impedance analysis. The measurements were then used to calculate body mass index (BMI), body fat mass index (BFMI), body adiposity index (BAI), the waist-hip ratio (WHR) and the waist-height ratio (WHtR). In the statistical analysis, Pearson's correlation coefficients and stepwise multiple regression analysis with backward elimination were used.
A direct relationship was established between IL-6 and CRP levels (r = 0.639; p < 0.05). Moreover, IL-6 significantly and positively correlated with hip and neck circumferences, BMI, BFMI, and BAI, as well as with VFR (r range 0.597–0.704; p < 0.05). The multiple regression analysis for IL-6 showed that the neck circumference was the only statistically significant independent variable (r² = 0.496; p < 0.05; SEE = 0.554 pg/ml).
The results suggest that of all popular indices of adiposity neck circumference is the best predictor of serum IL-6 concentration in the oldest old women without inflammation.
Physical Activity as a Modern Intervention in the Fight against Obesity-Related Inflammation in Type 2 Diabetes Mellitus and Gestational Diabetes
2023, Antioxidants
Therapeutic Activity of Green Tea Epigallocatechin-3-Gallate on Metabolic Diseases and Non-Alcoholic Fatty Liver Diseases: The Current Updates
2023, Nutrients
Chronic cannabis use is associated with altered monocyte phenotype, immune response, and depression in physically active individuals
2023, Canadian Journal of Physiology and Pharmacology

View all citing articles on Scopus

View full text

An exercise intervention without weight loss decreases circulating interleukin-6 in lean and obese men with and without type 2 diabetes mellitus

Abstract

Introduction

Section snippets

Subjects

Baseline subject characteristics

Discussion

Acknowledgments

Metabolism

Am J Clin Nutr

Metabolism

Diabetes Res Clin Pract

Metabolism

Metabolism

Biochim Biophys Acta

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

Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro

J Clin Endocrinol Metab

NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X

Diabetologia

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