Running from Disease: Molecular Mechanisms Associating Dopamine and Leptin Signaling in the Brain with Physical Inactivity, Obesity, and Type 2 Diabetes

Abstract

Physical inactivity is a primary contributor to diseases such as obesity, cardiovascular disease, and type 2 diabetes. Accelerometry data suggest that a majority of US adults fail to perform substantial levels of physical activity needed to improve health. Thus, understanding the molecular factors that stimulate physical activity, and physical inactivity, is imperative for the development of strategies to reduce sedentary behavior and in turn prevent chronic disease. Despite many of the well-known health benefits of physical activity being described, little is known about genetic and biological factors that may influence this complex behavior. The mesolimbic dopamine system regulates motivating and rewarding behavior as well as motor movement. Here, we present data supporting the hypothesis that obesity may mechanistically lower voluntary physical activity levels via dopamine dysregulation. In doing so, we review data that suggest mesolimbic dopamine activity is a strong contributor to voluntary physical activity behavior. We also summarize findings suggesting that obesity leads to central dopaminergic dysfunction, which in turn contributes to reductions in physical activity that often accompany obesity. Additionally, we highlight examples in which central leptin activity influences physical activity levels in a dopamine-dependent manner. Future elucidation of these mechanisms will help support strategies to increase physical activity levels in obese patients and prevent diseases caused by physical inactivity.

Microbiome and morbid obesity increase pathogenic stimulus diversity

“…Leptin is produced by adipocytes and promotes the synthesis of a-melanocyte-stimulating hormone (a-MSH) within the medial hypothalamus resulting in the inhibition of hunger. It further counteracts the hunger promotor, 36-amino acid neuropeptide (neuropeptide Y, NPY), within the lateral hypothalamus [144][145][146], which is released in the gut and the hypothalamus and N-arachidonoylethanolamine (anandamide, AEY) [147] and is synthesized by N-arachidonoyl phosphatidylethanolamine (NAPE) through an N-acyltransferase enzyme stimulating satiety [148].…”

Mapping brown adipose tissue based on fat water fraction provided by Z‐spectral imaging

“…O ver the recent years, the study of fat has attracted increasing interest of clinicians and researchers as it grew from being considered a simple energy storage tissue to a much more faceted organ secreting hormones involved in critical functions, from metabolism regulation to motivation and depression. 1,2 In particular, the last 10 years have seen the resurgence of the interest in brown adipose tissue (BAT). This peculiar kind of fat has a great significance in whole-body energy balance, given to its property of converting triglycerides and glucose into heat, through the nonshivering thermogenesis process.…”

Relationship of serum leptin with parameters of nutritional status and body composition among patients with stable course of cardiovascular disorders

“…However, work by Guerra et al [27] shows an increase in blood leptin concentration after one week of bed rest. Exercise habits also had an effect on muscle mass and handgrip strength, and leptin seems to take part in the central regulation of physical activity in a dopamine-dependent manner [12].…”

“…Leptin takes part in the long-term regulation of energy intake, and decreases appetite level in relation to energy storage (it is known as the satiety hormone) through the central inhibition of the secretion of orexigenic substances. Moreover, leptin induces activation of peripheral sympathetic nerve activity, leading to increased energy expenditure; it restores and regulates hypothalamic neuroendocrine axes, including the thyroid, gonadal, adrenocorticotropic hormone (ACTH)-cortisol and growth hormone axes [6,10]; plays a role in muscle-bone crosstalk [11], the central regulation of physical activity [12], age-related fat accumulation in muscles [13], and neurocognitive processes, emotions, and memory [6]; affects some of the pathophysiological processes in the cardiovascular system, such as the promotion of left ventricular hypertrophy, vascular remodeling, hypertrophy, angiogenesis, and the proliferation of neointimal and vascular smooth muscle cells; takes part in atherosclerosis processes [5,7]; and is recognized as a mediator inducing the survival, proliferation, invasion, migration, angiogenesis and anti-apoptosis of cancer cells, especially in patients with so-called obesity-related neoplasms (e.g. prostate, colorectal, and breast) [14].…”