The lateral hypothalamus: A site for integration of nutrient and fluid balance

This paper reviews seemingly obligatory relations between nutrient and fluid balance. A relatively novel neuronal pathway involving interplay between acetylcholine and the melanocortins, αMSH and AGRP in the arcuate nucleus (Arc) of the hypothalamus projecting to the lateral hypothalamus (LH) may bridge this gap. In the fasted condition, increased expression of MCH (due to muscarinic-3 receptor stimulation and low melanocortin tone) and neuronal release of MCH (via Orexin signaling) underlies a drive towards positive energy balance, increased B cell capacity to secrete insulin, and this is associated with optimal fluid homeostasis. A hypohydrated state is hypothesized to yield downregulation of leptin signaling (potentially via inhibitory effects of osmotic stress on mTOR), but osmotic stress may prevent MCH expression via the OVLT-SFO complex. If this occurs in an obese state, impaired pancreatic B cell capacity and peripheral insulin insensitivity as a result of hypohydration may underlie cardio-metabolic diseases.

Research highlights
► Obligatory, but largely unknown crosslinks exist between energy balance and fluid balance.
► Central cholinergic and neuropeptidergic (melanocortins, MCH) transmission may bridge this gap. Via these networks, leptin regulates whole body insulin action, fuel fluxes, and energy balance.
► It is proposed that these leptin actions are influenced by the neuronal hydrative state.
► Chronic mild osmotic stress may contribute to leptin resistance and cardiometabolic co-morbidities.