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Its role in the VMH of female mice remains to be defined, especially considering that this hypothalamic region is sexually dimorphic. We found that \u03b12\u03b4-1 depletion in SF1 neurons differentially affects glucose and lipid balance control and sympathetic tone in females compared to males. Mutant females show a modest increase in relative body weight gain when fed a high-fat diet (HFD) and normal energy expenditure, indicating that \u03b12\u03b4-1 is not a critical regulator of energy balance in females, similar to males. However, diminished \u03b12\u03b4-1 function in the VMH leads to enhanced glycemic control in females fed a chow diet, in contrast to the glucose intolerance reported previously in mutant males. Interestingly, the effects of \u03b12\u03b4-1 on glucose balance in females are influenced by diet. Accordingly, females but not males lacking \u03b12\u03b4-1 exhibit diminished glycemic control as well as susceptibility to hepatic steatosis when fed a HFD. Increased hepatic sympathetic tone and CD36 mRNA expression and reduced adiponectin levels underlie these diet-induced metabolic alterations in mutant females. The results indicate that \u03b12\u03b4-1 in VMH SF1 neurons critically regulates metabolic function through sexually dimorphic mechanisms. These findings are clinically relevant since metabolic alterations have been reported as a side effect in human patients prescribed gabapentinoid drugs, known to inhibit \u03b12\u03b4-1 function, for the treatment of seizure disorders, neuropathic pain, and anxiety disorders.<\/jats:p>","DOI":"10.1210\/endocr\/bqaa068","type":"journal-article","created":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T03:05:50Z","timestamp":1587956750000},"source":"Crossref","is-referenced-by-count":5,"title":["Sex-specific Effects of \u03b12\u03b4-1 in the Ventromedial Hypothalamus of Female Mice Controlling Glucose and Lipid Balance"],"prefix":"10.1210","volume":"161","author":[{"given":"Jennifer A","family":"Felsted","sequence":"first","affiliation":[{"name":"Graduate Program in Biochemical and Molecular Nutrition, Friedman School of Nutrition Science and Policy, Tufts University, Boston, 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