F. H. K. Kreier

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.

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.

Diabetes of the elderly and type 2 diabetes in younger patients: Possible role of the biological clock.

The increased prevalence of type 2 diabetes in the aged has been recognized for a long time. Within the last decades, a growing number of younger subjects and even children are prone to develop type 2 diabetes. In both groups, aged and young, the biological clock, located in the suprachiasmatic nucleus of the hypothalamus (SCN) is malfunctioning as evidenced by disturbed sleep cycles and altered circadian rhythms. While elderly patients have an impaired function of the SCN due to the degeneration of neurons, we propose that in younger subjects the clock loses its feeling for internal and external rhythms caused by the modern lifestyle. Sleeping late and less coupled with constant metabolic excess alter both internal and external environmental stimuli to the brain. In response to these alterations, the rhythm of the biological clock is disrupted which may lead to the metabolic syndrome and type 2 diabetes.