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Hypothalamic sensing of nutrients
Author(s) -
Rossetti Luciano
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a421-d
Subject(s) - hypothalamus , nutrient , nutrient sensing , endocrinology , medicine , endogeny , gluconeogenesis , metabolism , enzyme , diabetes mellitus , carbohydrate metabolism , arcuate nucleus , amino acid , biology , chemistry , biochemistry , signal transduction , ecology
Increased endogenous glucose production (GP) is the major determinant of fasting hyperglycaemia in diabetes mellitus. Here we put forward the postulate that the metabolism of macronutrients within specific hypothalamic nuclei is a primary biochemical sensor for nutrient availability, which in turn exerts a negative feedback on GP. We will present evidence in support of specific biochemical mechanisms by which fatty acids, glucose/lactate, and amino acids are sensed within the arcuate nuclei of the hypothalamus. We will also describe a partly overlapping pathway by which the sensing of these nutrients in the hypothalamus result in marked decreases in liver glucose fluxes and in the expression of gluconeogenic enzymes. We propose that this novel cross‐talk between brain and liver couples central nutrient sensing to peripheral nutrient production and its disruption may lead to fasting hyperglycaemia.