Chronic central neuropeptide Y infusion in normal rats: status of the hypothalamo-pituitary-adrenal axis, and vagal mediation of hyperinsulinaemia

Summary: Neuropeptide Y in the hypothalamus is a potent physiological stimulator of feeding, and may contribute to the characteristic metabolic defects of obesity when hypothalamic levels remain chronically elevated. Since corticosterone and insulin are important regulators of fuel metabolism, the longitudinal effects of chronic (6 days) intracerebroventricular infusion of neuropeptide Y in normal rats on the hypothalamo-pituitary-adrenal axis and on insulin secretion were studied. Neuropeptide Y-infused rats were either allowed to eat ad libitum, or were pair-fed with normophagic control rats. Neuropeptide Y increased the basal plasma concentrations of adrenocorticotropic hormone and corticosterone during the first 2 days of its intracerebroventricular infusion and increased cold stress-induced plasma adrenocorticotropic hormone concentrations. After 4-6 days of central neuropeptide Y infusion, however, basal plasma adrenocorticotropic hormone and corticosterone concentrations were no different from control values (except in ad libitum-fed rats in which corticosteronaemia remained elevated), they were unaffected by the stress of cold exposure, and the hypothalamic content of corticotropin-releasing factor immunoreactivity was significantly decreased. A state of hyperinsulinaemia was present throughout the 6 days of intracerebroventricular neuropeptide Y infusion, being more marked in the ad libitum-fed than in the pair-fed group. The proportions of insulin, proinsulin, and conversion intermediates in plasma and pancreas were unchanged. Hyperinsulinaemia of the pair-fed neuropeptide Y-infused rats was accompanied by muscle insulin resistance and white adipose tissue insulin hyperresponsiveness, as assessed by the in vivo uptake of 2-deoxyglucose. Finally, bilateral subdiaphragmatic vagotomy prevented both the basal and the marked glucose-induced hyperinsulinaemia of animals chronically infused with neuropeptide Y, demonstrating that central neuropeptide Y-induced hyperinsulinaemia is mediated by the parasympathetic nervous syste

Overfeeding, Autonomic Regulation and Metabolic Consequences

The autonomic nervous system plays an important role in the regulation of body processes in health and disease. Overfeeding and obesity (a disproportional increase of the fat mass of the body) are often accompanied by alterations in both sympathetic and parasympathetic autonomic functions. The overfeeding-induced changes in autonomic outflow occur with typical symptoms such as adiposity and hyperinsulinemia. There might be a causal relationship between autonomic disturbances and the consequences of overfeeding and obesity. Therefore studies were designed to investigate autonomic functioning in experimentally and genetically hyperphagic rats. Special emphasis was given to the processes that are involved in the regulation of peripheral energy substrate homeostasis. The data revealed that overfeeding is accompanied by increased parasympathetic outflow. Typical indices of vagal activity (such as the cephalic insulin release during food ingestion) were increased in all our rat models for hyperphagia. Overfeeding was also accompanied by increased sympathetic tone, reflected by enhanced baseline plasma norepinephrine (NE) levels in both VMH-lesioned animals and rats rendered obese by hyperalimentation. Plasma levels of NE during exercise were, however, reduced in these two groups of animals. This diminished increase in the exercise-induced NE outflow could be normalized by prior food deprivation. It was concluded from these experiments that overfeeding is associated with increased parasympathetic and sympathetic tone. In models for hyperphagia that display a continuously elevated nutrient intake such as the VMH-lesioned and the overfed rat, this increased sympathetic tone was accompanied by a diminished NE response to exercise. This attenuated outflow of NE was directly related to the size of the fat reserves, indicating that the feedback mechanism from the periphery to the central nervous system is altered in the overfed state.

The contribution of Swiss scientists to the assessment of energy metabolism

Although Switzerland is considered a small country, it has its share in discoveries, inventions and developments for the assessment of energy metabolism. This includes seminal contributions to respiratory and metabolic physiology and to devices for measuring energy expenditure by direct and indirect calorimetry in vivo in humans and small animals (as well as in vitro in organs/tissues), for the purpose of evaluating the basic nutritional requirements. A strong momentum came during World War II when it was necessary to evaluate the energy requirements of soldiers protecting the country by assessing their energy expenditure, as well as to determine the nutritional needs of the Swiss civil population in time of war when food rationing was necessary to ensure national neutrality and independence. A further impetus came in the 1970s at the start of the obesity epidemics, toward a better understanding of the metabolic basis of obesity, ranging from the development of whole-body concepts to molecular mechanisms. In a trip down memory lane, this review focuses on some of the earlier leading Swiss scientists who have contributed to a better understanding of the field

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

CMS physics technical design report : Addendum on high density QCD with heavy ions

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