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The VMH is a relatively large nucleus within the hypothalamus and can be anatomically categorised into three subdivisions: dorsal medial (VMHdm), central (VMHc) and ventral lateral (VMHvl).SF-1 neurones directly and indirectly project to neuronal sites such as the parabrachial nucleus, nucleus of the solitary tract and rostral ventrolateral medulla, which regulate SNS activity.Optogenic or chemogenic activation of SF-1 neurones alters SNS-dependent physiological responses, such as increases in heart rateand glucose levels.We recently found that exercise training increases the mRNA levels of SF-1 and putative SF-1 target genes in the mediobasal hypothalamus (which includes the VMH).They found that administration of ?-or ?-AdR antagonists in the VMH of exercising rats reciprocally altered circulating glucose and fatty acids without changing insulin levels.Follow-up studies found that injection of the anesthetic Marcain into the VMH during exercise impaired glucose mobilisation, whereas injection of the anesthetic lidocaine inhibited fatty acid oxidation.Interestingly, inhibition of VMH activity with ?-and ?-AdRs antagonists or lidocaine did not have an effect in sedentary animals.The VMH is required for adaptive energy expenditure in response to environmental challenges such as hypoglycaemia, .a high-fat diet (HFD) and ageing.For example, mice with gene specific manipulations in the VMH develop severe obesity and show impaired diet-induced thermogenesis only when fed a HFD.Additionally, muscarinic receptors in the VMH regulate body temperature and oxygen consumption in response to exercise.These studies demonstrate that VMH neurones contribute to the regulation of metabolism through the partitioning of energy substrates, energy expenditure and heat dissipation.This is consistent with studies showing that the VMH modulates fatty acid mobilisation and oxidation during exercise.Unexpectedly, deletion of SF-1 in the VMH also impaired exercise-induced increases in skeletal muscle mass and PGC-1?The SNS mediates VMH-regulated peripheral glucose uptake.mRNA expression.

The VMH is a relatively large nucleus within the hypothalamus and can be anatomically categorised into three subdivisions: dorsal medial (VMHdm), central (VMHc) and ventral lateral (VMHvl). Each VMH-subdivision has distinct and overlapping roles in the biological regulation of behaviour, reproduction and metabolism.
Recent studies utilising sophisticated genetic tools show that the main role of the VMH is to regulate energy expenditure and substrate utilisation. The VMH is required for adaptive energy expenditure in response to environmental challenges such as hypoglycaemia, .a high-fat diet (HFD) and ageing.For example, mice with gene specific manipulations in the VMH develop severe obesity and show impaired diet-induced thermogenesis only when fed a HFD.

Exercise is another metabolic challenge that disrupts homeostasis and this requires the rapid use and mobilisation of energy substrates to satisfy changing energy demands.

Exercise is a potent stimulator of sympathetic nervous system (SNS) activity and catecholamine secretion, increasing lipolysis, glycogenolysis and increasing blood flow to enhance nutrient delivery and waste removal.

The SNS mediates VMH-regulated peripheral glucose uptake. Microinjections of leptin or orexin into the VMH increase skeletal muscle glucose uptake and these effects are blunted by adrenergic receptors (AdR) antagonists. Intriguingly, βAdR agonists potently increase skeletal muscle mass and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) mRNA expression. Not surprisingly, moderate and high intensity exercise increases catecholamines in humans and rodents. Moreover, βAdR2 antagonists can suppress exercise-induced PGC-1α mRNA and other transcriptional signals that regulate glucose, fatty acid and protein metabolism in skeletal muscle.

Scheurink previously investigated the role of the VMH in the regulation of metabolism in response to exercise. They found that administration of α-or β-AdR antagonists in the VMH of exercising rats reciprocally altered circulating glucose and fatty acids without changing insulin levels.Follow-up studies found that injection of the anesthetic Marcain into the VMH during exercise impaired glucose mobilisation, whereas injection of the anesthetic lidocaine inhibited fatty acid oxidation.Interestingly, inhibition of VMH activity with α-and β-AdRs antagonists or lidocaine did not have an effect in sedentary animals. In line with these findings, stimulating the VMH in sedentary animals has repeatedly been shown to elevate circulating glucose levels and enhance glucose uptake by skeletal muscle. Additionally, muscarinic receptors in the VMH regulate body temperature and oxygen consumption in response to exercise.These studies demonstrate that VMH neurones contribute to the regulation of metabolism through the partitioning of energy substrates, energy expenditure and heat dissipation. However, questions still remain concerning which specific neuronal populations within the VMH, as well as what mechanistic signals within these neurones, are important for acute and chronic metabolic adaptations to exercise training.

Although the VMH-SNS axis is likely the key regulator of skeletal muscle adaptions to exercise, whether SF-1 neurones regulate SNS activity during/post exercise is still an open question. SF-1 neurones directly and indirectly project to neuronal sites such as the parabrachial nucleus, nucleus of the solitary tract and rostral ventrolateral medulla, which regulate SNS activity.Optogenic or chemogenic activation of SF-1 neurones alters SNS-dependent physiological responses, such as increases in heart rateand glucose levels.We recently found that exercise training increases the mRNA levels of SF-1 and putative SF-1 target genes in the mediobasal hypothalamus (which includes the VMH). Mice lacking SF-1 from the VMH had a blunted response to training-induced improvements in whole body energy expenditure, catecholamine release, fat loss and body composition. This is consistent with studies showing that the VMH modulates fatty acid mobilisation and oxidation during exercise.Unexpectedly, deletion of SF-1 in the VMH also impaired exercise-induced increases in skeletal muscle mass and PGC-1α mRNA expression.