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Publication
Insulin signaling in LepR cells modulates fat and glucose homeostasis
independent of leptin.
Authors Borges BC, Han X, Allen SJ, Garcia-Galiano D, Elias CF
Submitted By Submitted Externally on 11/24/2019
Status Published
Journal American journal of physiology. Endocrinology and metabolism
Year 2019
Date Published 1/1/2019
Volume : Pages 316 : E121 - E134
PubMed Reference 30376348
Abstract Hypothalamic neurons detect changes in circulating hormones such as leptin and
insulin and put forward outputs to sustain energy and glucose homeostasis.
Because leptin and insulin receptors colocalize in ~40-60% of neurons in the
hypothalamus, we characterized the metabolic phenotype of mice with selective
deletion of the insulin receptor (InsR) in LepR cells. LR?InsR mice presented no
difference in body weight and insulin levels but increased fat mass. In the
light phase, LR?InsR mice exhibited increased food intake, locomotor activity,
carbon dioxide production, and respiratory exchange rate. These mice showed
reduced fat oxidation and reduced expression of cluster of differentiation 36
and AMP-activated protein kinase-a1 in the liver, increased glucose oxidation in
the light phase, and overall reduced basal glucose levels. To verify the impact
of InsR deletion in LepR cells in obesity, we generated ob/ ob InsRfl, ob/ ob
LRcre, and ob/ ob LR?InsR mice. The ob/ ob LR?InsR mice had higher body weight,
fat mass, and expression of genes related to fat metabolism in the liver. No
difference in food intake despite increased neuropeptide Y and agouti-related
peptide expression, and no difference in energy expenditure, fat, or glucose
oxidation was found in ob/ ob LR?InsR compared with LRcre or LR?InsR controls.
Remarkably, basal glucose levels were reduced, and the expression of genes
associated with glucose metabolism in the liver was higher. Insulin signaling in
LepR cells is required for the proper fat and glucose oxidation. These effects
are independent of leptin given that the leptin-deficient ob/ ob LR?InsR mice
also presented reduced glycemia and higher adiposity. The mechanisms underlying
these responses remain to be unveiled.




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