title: SOCS3 expression within leptin receptor-expressing cells regulates food intake and leptin sensitivity but does not affect weight gain in pregnant mice consuming a high-fat diet.
abstract: Pregnancy induces transitory metabolic changes including increases in food intake and body fat deposition, as well as leptin and insulin resistance. Recent findings have suggested that increased hypothalamic expression of suppressor of cytokine signaling-3 (SOCS3) is a key mechanism responsible for triggering those metabolic adaptations. Because obesity is a risk factor for gestational metabolic imbalances, we aimed to study the role of SOCS3 during pregnancy in obese mice. Female mice carrying a deletion of SOCS3 in leptin receptor-expressing cells (SOCS3 KO mice) were exposed to a chronic high-fat diet (HFD), and we then studied their energy balance and glucose homeostasis during pregnancy. SOCS3 deletion did not prevent diet-induced obesity or changes in body weight and adiposity observed during pregnancy. However, the typical increase in food intake during mid- and late-pregnancy was blunted in SOCS3 KO females. We also observed a slight improvement in glucose homeostasis and increased leptin sensitivity in the arcuate nucleus of the hypothalamus in pregnant SOCS3 KO mice on HFD. Despite this, SOCS3 KO mice had an increased number of uterine reabsorptions and fewer fetuses compared to the controls. Compared to control animals, a reduction in proopiomelanocortin and an increase in oxytocin mRNA levels were observed in the hypothalamus of pregnant SOCS3 KO mice. In contrast to previous studies using lean animals, conditional SOCS3 ablation did not prevent major gestational metabolic changes in diet-induced obese mice. Our findings contribute to the understanding of the role of SOCS3 in mediating pregnancy-induced metabolic adaptations.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil. Electronic address: thaizampieri@gmail.com.
authors.forename: Thais Tessari
authors.initials: TT
authors.lastname: Zampieri
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil. Electronic address: tiagoeugenioo@gmail.com.
authors.forename: Tiago Eugênio Oliveira
authors.initials: TE
authors.lastname: da Silva
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil. Electronic address: deborah.romeu@gmail.com.
authors.forename: Deborah
authors.initials: D
authors.lastname: de Paula Romeu
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil. Electronic address: andrea@icb.usp.br.
authors.forename: Andréa da Silva
authors.initials: AS
authors.lastname: Torrão
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil. Electronic address: jdonato@icb.usp.br.
authors.forename: Jose
authors.initials: J
authors.lastname: Donato
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects*; D004435:Eating / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005951:Glucose Tolerance Test; D007031:Hypothalamus / Q000378:metabolism* / Q000473:pathology; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism*; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D020738:Leptin; D012333:RNA, Messenger; D054411:Receptors, Leptin; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein
keywords: Hypothalamus; Leptin; Leptin resistance; Obesity; Pregnancy; Suppressor of cytokine signaling