Arun Maharaj

Brain‐Derived Neurotrophic Factor and Substrate Utilization Following Acute Aerobic Exercise in Obese Individuals

Brain‐derived neurotrophic factor (BDNF) serves as a vital regulator of neuronal proliferation and survival, and has been shown to regulate energy homeostasis, glucose metabolism and body weight maintenance. Elevated concentrations of plasma BDNF have been associated with obesity and type 2 diabetes mellitus. Acute aerobic exercise transiently increases circulating BDNF, potentially correcting obesity‐related metabolic impairment. The present study aimed to compare acute aerobic exercise elicited BDNF responses in obese and normal‐weight subjects. Furthermore, we aimed to investigate whether acute exercise‐induced plasma BDNF elevations would be associated with improved indices of insulin resistance, as well as substrate utilization [carbohydrate oxidation (CHOoxi) and fat oxidation (FAToxi)]. Twenty‐two healthy, untrained subjects [11 obese (four men and seven women; age = 22.91 ± 4.44 years; body mass index = 35.72 ± 4.17 kg/m2) and 11 normal‐weight (five men and six women; age = 23.27 ± 2.24 years; body mass index = 21.89 ± 1.63 kg/m2)] performed 30 min of continuous submaximal aerobic exercise at 75% maximal oxygen consumption. Our analyses showed that the BDNF response to acute aerobic exercise was similar in obese and normal‐weight subjects across time (time: P = 0.015; group: P = not significant) and was not associated with indices of IR. Although no differences in the rates of CHOoxi and FAToxi were found between both groups, total relative energy expenditure was significantly lower in obese subjects compared to normal‐weight subjects (3.53 ± 0.25 versus 5.59 ± 0.85; P < 0.001). These findings suggest that acute exercise‐elicited BDNF elevation may not be sufficient to modulate indices of IR or the utilization of either carbohydrates or fats in obese individuals.

The impact of acute aerobic exercise on chitinase 3-like protein 1 and intelectin-1 expression in obesity.

Chitinase 3-like 1 (CHI3L1) and intelectin 1 (ITLN-1) recognize microbial N-acetylglucosamine polymer and galactofuranosyl carbohydrates, respectively. Both lectins are highly abundant in plasma and seem to play pro- and anti-inflammatory roles, respectively, in obesity and inflammatory-related illnesses. The aim of this study was to examine whether plasma levels of these lectins in obese subjects are useful for monitoring inflammatory conditions immediately influenced by acute aerobic exercise. Plasma interleukin-6, a pro-inflammatory cytokine, was also examined. Twenty-two (11 obese and 11 normal-weight) healthy subjects, ages 18–30 years, were recruited to perform a 30 min bout of acute aerobic exercise at 75% VO2max. We confirmed higher baseline levels of plasma CHI3L1, but lower ITLN-1, in obese subjects than in normal-weight subjects. The baseline levels of CHI3L1 were negatively correlated with cardiorespiratory fitness (relative VO2max). However, when controlled for BMI, the relationship between baseline level of CHI3L1 and relative VO2max was no longer observed. While acute aerobic exercise elicited an elevation in these parameters, we found a lower ITLN-1 response in obese subjects compared to normal-weight subjects. Our study clearly indicates that acute aerobic exercise elicits a pro-inflammatory response (e.g. CHI3L1) with a lower anti-inflammatory effect (e.g. ITLN-1) in obese individuals. Furthermore, these lectins could be predictors of outcome of exercise interventions in obesity-associated inflammation.

Acute aerobic exercise mediates G protein-coupled receptor kinase 2 expression in human PBMCs

AIMS G protein-coupled receptor kinase 2 (GRK2), a cytosolic enzyme desensitizing G protein-couple receptors (e.g., β-adrenergic receptors [β-ARs]), is involved in regulation of hypertension, congestive heart failure, and inflammatory response. Since cellular GRK2 levels change quickly in response to exogenous/endogenous stimuli, this study examined whether GRK2 levels in human peripheral blood mononuclear cells (PBMCs) would increase during acute aerobic exercise and be associated with plasma IL-6 and cardiorespiratory fitness levels. MAIN METHODS Eighteen subjects (8 men and 10 women), ages 18 to 30 years, were recruited to perform a 30-minute bout of acute aerobic exercise at 75% VO2max. KEY FINDINGS Our results demonstrated that women exhibited significantly greater exercise-induced GRK2 expression in PBMCs compared to men. IL-6 modulation is independent of GRK2 expression. Furthermore, the percent change in GRK2 expression was negatively correlated with cardiorespiratory fitness levels (relative VO2max), but not plasma IL-6. SIGNIFICANCE Acute aerobic exercise induces a greater GRK2 expression in women than men, while increased cardiorespiratory fitness is associated with exercise-induced GRK2 expression in PBMCs. Gender could be a contributor to regulate this GRK2 responsiveness to acute aerobic exercise.

Exercise reduced pentraxin 3 levels produced by endotoxin-stimulated human peripheral blood mononuclear cells in obese individuals

The purpose of this study was to determine whether obesity would reduce the capacity of peripheral blood mononuclear cells (PBMCs) to produce the anti-inflammatory protein pentraxin 3 (PTX3) in response to ex vivo stimulation with lipopolysaccharide (LPS), and if acute aerobic exercise would enhance this PTX3 production capacity. In addition, the inter-relationships of LPS-induced PTX3 with the inflammatory cytokines (interleukin 6 [IL-6], IL-10, and tumor necrosis factor alpha) were examined. Twenty-one healthy subjects (10 obese and 11 normal-weight) performed an acute bout of aerobic exercise at 75% VO2max. The capacity of PBMCs to produce PTX3 ex vivo following LPS stimulation was the same in obese and normal-weight subjects at rest, and decreased equally in both subject groups following acute aerobic exercise. This is in contrast to plasma PTX3, which is lower in obese subjects at rest and increased equally in both obese and normal-weight subjects following exercise. In addition, ex vivo PTX3 production was positively associated with IL-6 and IL-10 in response to acute aerobic exercise (r = 0.686, P = 0.020; r = 0.744, P = 0.009, respectively) in normal-weight, but not in obese individuals (r = 0.429, P = 0.249; r = 0.453, P = 0.189, respectively). These findings indicate that concentrations of PTX3 observed in plasma are relatively independent of those produced by PBMCs ex vivo and the mechanisms associated with PTX3-mediated anti-inflammatory signaling may differ during obesity. Impact statement Our laboratory has previously demonstrated that obese individuals present with lower plasma concentrations of the anti-inflammatory protein pentraxin 3 (PTX3), whereas acute aerobic exercise increases plasma PTX3 levels similarly compared to normal-weight individuals. As a follow-up, the present study demonstrates that PBMCs isolated from obese and normal-weight individuals produce comparable amounts of PTX3 ex vivo in response to lipopolysaccharide (LPS). Furthermore, given that acute aerobic exercise reduced the ex vivo production of PTX3 in both groups, our results clearly indicate that plasma PTX3 levels are relatively independent of those produced by PBMCs ex vivo. In addition, our findings suggest that the mechanisms associated with PTX3-mediated production of the anti-inflammatory cytokine interleukin 10 may be impaired in obese individuals, and thus provides a key finding necessary for the elucidation of PTX3’s role in the mediation of anti-inflammatory profiles and the subsequent amelioration of inflammatory disease during obesity.