Autonomic nervous system dysfunction in obesity and Prader-Willi syndrome: current evidence and implications for future obesity therapies.

The autonomic nervous system (ANS) controls essential functions like breathing, heart rate, digestion, body temperature and hormone levels. Evidence suggests that ANS dysfunction is associated with adult and childhood obesity and plays a role in the distribution of total body fat and the development of obesity-related complications in humans. This review summarizes our current understanding of ANS involvement in the pathogenesis of obesity and Prader-Willi syndrome. Available evidence of ANS dysfunction in the control of energy balance is limited and, in some cases, contradictory. Further investigation in this area is warranted in order to better understand the important contributions of the ANS to regulation of body fat, development of obesity and its comorbidities. Results from these studies will guide the development of novel obesity therapeutics targeting specific ANS dysfunction.

SCN outputs and the hypothalamic balance of life.

The circadian clock in the suprachiasmatic nucleus (SCN) is composed of thousands of oscillator neurons, each dependent on the cell-autonomous action of a defined set of circadian clock genes. Still, the major question remains how these individual oscillators are organized into a biological clock producing a coherent output able to time all the different daily changes in behavior and physiology. In the present review, the authors discuss the anatomical connections and neurotransmitters used by the SCN to control the daily rhythms in hormone release. The efferent SCN projections mainly target neurons in the medial hypothalamus surrounding the SCN. The activity of these preautonomic and neuroendocrine target neurons is controlled by differentially timed waves of, among others, vasopressin, GABA, and glutamate release from SCN terminals. Together, the data on the SCN control of neuroendocrine rhythms provide clear evidence not only that the SCN consists of phenotypically (i.e., according to neurotransmitter content) different subpopulations of neurons but also that subpopulations should be distinguished (within phenotypically similar groups of neurons) based on the acrophase of their (electrical) activity. Moreover, the specialization of the SCN may go as far as a single body structure, that is, the SCN seems to contain neurons that specifically target the liver, pineal, and adrenal.

HIV-associated adipose redistribution syndrome as a selective autonomic neuropathy.

Abnormal body-fat distribution in HIV-1-associated adipose redistribution syndrome (HARS) remains unexplained at present. White adipose tissue is controlled by humoral factors and by neural regulation. Sympathetic innervation stimulates lipolysis, whereas parasympathetic innervation has an anabolic influence on white adipose tissue. Results of neuroanatomical studies showed a clear somatotopy with respect to autonomic control of white adipose tissue by both the sympathetic and parasympathetic branch, with separate sets of autonomic neurons innervating either the subcutaneous or the visceral fat compartment. Thus, the CNS is likely to be a key player in regulation of body-fat distribution. We propose that HARS is mediated by effects of antiretroviral treatment on the CNS and could indicate a change in autonomic balance resulting in redistribution of adipose tissue.

White adipose tissue: getting nervous.

Neuroendocrine research has altered the traditional perspective of white adipose tissue (WAT) as a passive store of triglycerides. In addition to fatty acids, WAT produces many hormones and can therefore be designated as a traditional endocrine gland actively participating in the integrative physiology of fuel and energy metabolism, eating behaviour and the regulation of hormone secretion and sensitivity. WAT is controlled by humoral factors, para- and intracrine factors and by neural regulation. Sympathetic nerve fibres innervate WAT and stimulate lipolysis, leading to the release of glycerol and free fatty acids. In addition, recent research in rats has clearly shown a functional parasympathetic innervation of WAT. There appears to be a distinct somatotopy within the parasympathetic nuclei: separate sets of autonomic neurones in the brain stem innervate either the visceral or the subcutaneous fat compartment. We therefore propose that the central nervous system (CNS) plays a major role in the hitherto unexplained regulation of body fat distribution. Parasympathectomy induces insulin resistance with respect to glucose and fatty acid uptake in the innervated fat depot and has selective effects on local hormone synthesis. Thus, the CNS is involved not only in the regulation of hormone production by WAT, but also in its hormone sensitivity. The developments in this research area are likely to increase our insights in the pathogenesis of metabolic disorders such as hypertriglyceridemia, diabetes mellitus type 2 and lipodystrophy syndromes.

[Adipose tissue: an innervated endocrine gland]. / Vetweefsel: een geïnnerveerde endocriene klier.

Until recently, adipose tissue was considered to function as a passive store of triglycerides and therefore of calories. Fascinating research over the past ten years has altered this traditional perspective. Adipose tissue has been shown to produce hormones. Leptin was discovered in 1994; one of its main functions is to adapt the organism to starvation. Sympathetic nerve fibres were shown to innervate adipose tissue and to facilitate lipolysis leading to the release of glycerol and free fatty acids. In addition, parasympathetic innervation of adipose tissue was recently demonstrated, with anabolic effects. Different sets of autonomic neurons in the brain stem appear to innervate either the abdominal or the subcutaneous fat compartment. This may be the anatomical substrate for the hitherto unexplained regulation of body fat distribution (subcutaneous versus intra-abdominal). Moreover, fat distribution under physiological conditions (sex steroids, glucocorticoids) and pathological conditions (e.g., AIDS lipodystrophy, Cushing syndrome) might be mediated via the central nervous system. The developments in this research area have the potential to increase our insights into the pathogenesis of metabolic disorders such as hypertriglyceridaemia and type-2 diabetes mellitus.