SOCS3 ablation in SF1 cells causes modest metabolic effects during pregnancy and lactation. (4th December 2017)

• Record Type: Journal Article
• Authors: Ramos-Lobo, Angela M.; Teixeira, Pryscila D.S.; Furigo, Isadora C.; Donato, Jose
• Is Part Of: Neuroscience. Volume 365(2017)
• Page Start: 114
• Page End: 124
• Publication Date: 2017-12-04
• Subjects: 3V third ventricle -- AgRP agouti-related peptide -- ARH arcuate nucleus of the hypothalamus -- CART cocaine and amphetamine regulated transcript -- CRH corticotropin-releasing hormone -- fx fornix -- GTT glucose tolerance test -- ITT insulin tolerance test -- KPBS 0.02 M potassium PBS, pH 7.4 -- LepR leptin receptor -- MCH melanin-concentrating hormone -- MPO median preoptic area -- NPY neuropeptide Y -- NTS nucleus of the solitary tract -- ORX orexin -- OXT oxytocin -- PMv ventral premammillary nucleus -- POMC proopiomelanocortin -- pSTAT3 phosphorylation of the signal transducer and activator of transcription 3 -- RCA retrochiasmatic area -- SF1 steroidogenic factor-1 -- SOCS3 suppressor of cytokine signaling 3 -- VMH ventromedial nucleus of the hypothalamus -- VMHc central part of the VMH -- VMHdm dorsomedial part of the VMH -- VMHvl ventrolateral part of the VMH; gestation -- cytokine receptor -- hypothalamus -- energy balance -- food intake -- glucose homeostasis; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2017.09.048
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: SF1 is expressed in 81% of leptin-responsive neurons of the VMH. SOCS3 ablation in SF1 cells increases leptin sensitivity in the VMH of pregnant mice. SOCS3 ablation in SF1 cells does not prevent pregnancy-induced hyperphagia and weight gain. SOCS3 ablation in SF1 cells causes glucose intolerance during pregnancy. SF1 SOCS3 KO mice have lower body weight during mid and late lactation. Abstract: Previous studies have shown that leptin resistance is a key feature that leads to gestational metabolic adaptions. We hypothesized that leptin sensitivity in the ventromedial nucleus of the hypothalamus (VMH) plays a critical role regulating gestational metabolic changes. In the present study, we generated a mouse model carrying ablation of the suppressor of cytokine signaling 3 (SOCS3) in steroidogenic factor-1 (SF1) cells, which include the VMH, in order to investigate whether increased leptin sensitivity in this neuronal population prevents at least part of the metabolic changes typically observed during gestation and lactation. As predicted by the inhibitory effects of SOCS3 in leptin signaling, pregnant SF1 SOCS3 KO mice exhibited increased leptin sensitivity in the VMH, since an acute leptin injection induced a 95% increase in the STAT3 phosphorylation in this nucleus, compared to control animals ( p = 0.02). Despite that, SF1 SOCS3 KO mice showed similar weight gain, food intake, hypothalamic neuropeptide expression and serum leptin levels during pregnancy compared to control littermates. Unexpectedly, SF1 SOCS3 KO mice exhibited glucose intolerance during pregnancy. SF1 SOCS3 KO mice also presented a lower body weight (−3%; p < 0.05) during mid and late lactation, although food intake, litter size and offspring growth were not affected. Our findings suggest that increased leptin sensitivity in the VMH causes modest metabolic effects and is not sufficient to prevent major metabolic adaptations of pregnancy and lactation.