Low Central Nervous System Serotonergic Responsivity Is Associated with the Metabolic Syndrome and Physical Inactivity

Abstract

The metabolic syndrome, recognized by the co-occurrence of general or abdominal obesity, hypertension, dyslipidemia, insulin resistance, and dysglycemia, appears to involve disturbances in metabolism, autonomic function, and health-related behaviors. However, physiological processes linking the components of the metabolic syndrome remain obscure. The current study examined associations of central nervous system serotonergic function with each metabolic syndrome risk variable, the metabolic syndrome, and physical activity. The subjects were 270 adult volunteers who participated in a study of cardiovascular disease risk factors and neurobehavioral functioning. Central serotonergic responsivity was indexed as the prolactin (PRL) response evoked by the serotoninreleasing agent, fenfluramine. Across the sample, low PRL response was associated with greater body mass index, higher concentrations of triglycerides, glucose, and insulin, higher systolic and diastolic blood pressure, greater insulin resistance, and less physical activity (P < 0.03-0.001). There also existed an inverse linear relationship between PRL response and the number of metabolic syndrome risk factors individuals possessed (P for trend ‫؍‬ 0.002). Finally, a 1 SD decline in PRL response was associated with an odds ratio for the metabolic syndrome of 2.05 (95% confidence interval, 1.10 -3.

Variations in tryptophan hydroxylase 2 linked to decreased serotonergic activity are associated with elevated risk for metabolic syndrome in depression

“…29,30,63 Furthermore, the serotonergic system has been shown to be involved in appetite and weight regulation and to modify the risk for metabolic disorders, as previous studies reported reduced CSF serotonin levels and decreased CNS serotonergic responsivity in MetS and obesity. 26,28 On the other hand, treatment with SSRIs decreases appetite and induces weight loss, 25,64 suggesting that dysregulation in central serotonergic system is important in obesity and MetS.…”

“…In this context, disturbances in brain serotonin system have been suggested to be important in the pathophysiology of both MD and metabolic disorders. [25][26][27] Lower serotonergic activity in the central nervous system (CNS) has been associated with both metabolic disorders 26,28 and MD. 29,30 Furthermore, selective serotonin reuptake inhibitors (SSRIs) have been shown to be successful for the treatment of MD, 31 metabolic disorders 32,33 and presumably for the prevention of cardiovascular morbidity and mortality, 34 emphasizing the importance of the serotonergic system in the pathophysiology of MetS and MD.…”

Lack of the serotonin transporter in mice reduces locomotor activity and leads to gender-dependent late onset obesity

“…36 In humans, reduced central 5-HT responsivity leads to physical inactivity and promotes the development of a metabolic syndrome. 37 A decline in physical activity, in turn, is supposed to underlie middle-age weight gain. 38 Here, we observed decreased motor activity in 5-HTT ko mice already at a young age.…”

Effects of Ovarian Steroids and Raloxifene on Proteins that Synthesize, Transport, and Degrade Serotonin in the Raphe Region of Macaques

“…Serotonin is now recognized as playing a regulatory role in an ever-growing number of autonomic functions (Dedeoglu and Fisher, 1994), cognitive domains (Meneses, 1999), affective, anxiety, and stress-related disorders (Lesch et al, 1996;Shively et al, 1997;Clement and Chapouthier, 1998;Shively et al, 2003), and even metabolic syndromes (Muldoon et al, 2004). As such, the serotonin neural system is a target of pharmacotherapies, steroid hormones, cytokines, neuropeptides, and growth factors, all of which impact the generation and efficacy of serotonin neurotransmission.…”