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GRP78 in the VMH modulates BAT and WAT. Over-expression of GRP78 specifically in the VMH ameliorates hypothalamic ER stress in rodent obese models leading to weight loss, reduced hepatic steatosis and improved insulin and leptin sensitivity. The action of GRP78 in the VMH is mediated by a feeding-independent mechanism involving increased tone of the sympathetic nervous system (SNS), increased BAT thermogenesis and stimulation browning of WAT.
