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Biomedical subjects

H Frankish

Publications and source records attributed to H Frankish.

23 records · Page 2Linked to original sources
PubMed1996

Relationships between hypothalamic neuropeptide Y and food intake in the lactating rat.

NPYergic neurons in the hypothalamic arcuate nucleus (ARC) that project to the paraventricular nucleus (PVN) are postulated to regulate food intake and energy balance. This projection is overactive in lactation and is thought to drive hyperphagia in this condition. We have explored further the relationship between hypothalamic NPY and food intake in lactation and tested the hypothesis that hypoinsulinemia is the stimulus to NPY neuronal activity. Compared with nonlactating controls (n = 10), freely fed lactating rats (n = 9) showed significantly increased (p < 0.05) NPY levels in the ARC and medial preoptic area (MPO), but there was no significant increase in whole hypothalamic NPY mRNA levels. Lactating rats (n = 8) that were restricted to control rats' food intake for 3 days showed generally higher hypothalamic NPY levels, with significantly higher concentrations than controls (p < 0.05) in the ARC, MPO, PVN, and lateral hypothalamic area (LHA); NPY mRNA levels were also significantly increased (p < 0.05). Across all three experimental groups, there was a significant inverse correlation between plasma insulin concentration and hypothalamic NPY mRNA levels (r = -0.39, p < 0.01). We conclude that the ARC-PVN projection is overactive in lactation and that this is not a consequence of hyperphagia. Hypoinsulinemia may stimulate these neurons, as it is thought to do in other conditions of energy deficit.

Animals↗
PubMed1996

Dissociation of hypothalamic NPY from BAT uncoupling protein mRNA in rats exposed to 24 h thermoneutrality.

Neuropeptide Y (NPY) is increasingly considered to be involved in the central regulation of energy balance. Our previous studies suggest that hypothalamic NPY neurons of the arcuatoparaventricular (ARC-PVN) projection are inhibited in association with the marked increases in brown adipose tissue (BAT) thermogenesis and uncoupling protein (UCP) gene expression in rats exposed to cold. We therefore hypothesized that the NPYergic ARC-PVN system would be activated in a thermoneutral environment, when energy expenditure falls to a minimum, and that this activation could mediate the fall in BAT activity. We measured regional hypothalamic NPY concentrations, hypothalamic NPY receptor binding, and NPY mRNA together with UCP mRNA levels in rats exposed to thermoneutrality (29 degrees C) for 24 h. At thermoneutrality, UCP mRNA levels fell to 42% of those in controls maintained at 22 degrees C, but there were no significant changes in hypothalamic NPY or NPY mRNA levels or in NPY receptor binding. We conclude that the fall in UCP mRNA expression occurring under short-term thermoneutral condition is mediated by neuroendocrine mechanisms other than increased activity of hypothalamic NPY neurons.

Adipose Tissue, Brown↗
PubMed1994

Neuropeptide Y and energy balance: one way ahead for the treatment of obesity?

Obesity is a vast and ever-expanding problem in affluent societies, which we have so far failed to confront. Over 20% of Western European and North American adults are overweight to a degree which may potentially shorten their life expectancy. Obesity has well-known associations with non-insulin-dependent diabetes (NIDDM), hypertension, dyslipidaemia and coronary heart disease, as well as less obvious links with diseases such as osteoarthrosis and various malignancies; it also causes considerable problems through reduced mobility and decreased quality of life. The overall financial burden of obesity is impossible to calculate precisely, but may account for 6-8% of total health-care expenditure in North America [1] (similar estimates probably apply to Western Europe). Obesity is difficult to treat and many patients remain obstinately overweight despite our best efforts. The available options range from behavioural therapy to gastrointestinal surgery and include numerous drugs designed to suppress appetite or increase energy expenditure. As in many other areas of medicine, the length and diversity of this list are reliable signs that effective treatment is still beyond our reach. This article argues that new anti-obesity drugs may emerge from recent advances in understanding the control of energy balance in rodents. The discussion is structured around neuropeptide Y (NPY), a major brain peptide which at present appears to be important in regulating energy balance and seems a promising candidate for therapeutic exploitation.

Animals↗