Changes in the Brain-Derived Neurotrophic Factor Are Associated with Improvements in Diabetes Risk Factors after Exercise Training in Adolescents with Obesity: The HEARTY Randomized Controlled Trial

Jeremy J Walsh,Denis Prud’Homme,Ronald J Sigal,Stasia Hadjiyannakis,Martin Holcik,Steve Doucette,Angela S Alberga,Amedeo D’Angiulli,Gary S Goldfield,Katie Gunnell,Jameason D Cameron,Glen P Kenny

doi:10.1155/2018/7169583

Abstract

Obesity in youth increases the risk of type 2 diabetes (T2D), and both are risk factors for neurocognitive deficits. Exercise attenuates the risk of obesity and T2D while improving cognitive function. In adults, these benefits are associated with the actions of the brain-derived neurotrophic factor (BDNF), a protein critical in modulating neuroplasticity, glucose regulation, fat oxidation, and appetite regulation in adults. However, little research exists in youth. This study examined the associations between changes in diabetes risk factors and changes in BDNF levels after 6 months of exercise training in adolescents with obesity. The sample consisted of 202 postpubertal adolescents with obesity (70% females) aged 14–18 years who were randomized to 6 months of aerobic and/or resistance training or nonexercise control. All participants received a healthy eating plan designed to induce a 250/kcal deficit per day. Resting serum BDNF levels and diabetes risk factors, such as fasting glucose, insulin, homeostasis model assessment (HOMA-B—beta cell insulin secretory capacity) and (HOMA-IS—insulin sensitivity), and hemoglobin A1c (HbA1c), were measured after an overnight fast at baseline and 6 months. There were no significant intergroup differences on changes in BDNF or diabetes risk factors. In the exercise group, increases in BDNF were associated with reductions in fasting glucose (β = −6.57, SE = 3.37, p = 0.05) and increases in HOMA-B (β = 0.093, SE = 0.03, p = 0.004) after controlling for confounders. No associations were found between changes in diabetes risk factors and BDNF in controls. In conclusion, exercise-induced reductions in some diabetes risk factors were associated with increases in BDNF in adolescents with obesity, suggesting that exercise training may be an effective strategy to promote metabolic health and increases in BDNF, a protein favoring neuroplasticity. This trial is registered with ClinicalTrials.gov NCT00195858, September 12, 2005 (funded by the Canadian Institutes of Health Research).

Highlights

Pediatric obesity currently affects 13–20% of children and youth in Westernized countries [1, 2]
This study investigated the independent associations between changes in serum brain-derived neurotrophic factor (BDNF), diabetes risk factors, and body composition following a 6-month exercise intervention in adolescents with obesity
The main findings from this study were (a) changes in some diabetes risk factors, most notably fasting glucose and beta cell insulin secretory capacity (HOMA-B), were stronger independent predictors of exercise-induced changes in BDNF than changes in body composition and (b) there was no relationship between anthropometric variables and BDNF at baseline or following the 6-month intervention period

Summary

Introduction

Pediatric obesity currently affects 13–20% of children and youth in Westernized countries [1, 2]. Obesity is associated with a myriad of deleterious health outcomes, including diminished neurocognitive function in childhood [3], an increased risk of Alzheimer’s disease, and dementia later in life [4], possibly due to increased inflammatory cytokines which have systemic effects linked to glycemic dysregulation and the initiation of type 2 diabetes (T2D) pathology [5]. Recurrent hyperglycemia is associated with adverse structural brain outcomes, including reduced gray and white matters [9], suggesting that improving metabolic regulation early in life is important for long-term brain health. Low circulating BDNF is associated with both neurological and metabolic conditions including, major depressive disorder [18], Alzheimer’s disease [19], obesity [20, 21], and T2D [22]. BDNF-haploinsufficient mice are obese and diabetic and exhibit hyperphagic behavior [24], and expression of the BDNF gene variant (Val66Met) is significantly associated with measures of obesity in human pediatric [20] and adult cohorts [21]

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