TY - JOUR

T1 - Sex Differences in Liver, Adipose Tissue, and Muscle Transcriptional Response to Fasting and Refeeding in Mice

AU - Bazhan, Nadezhda

AU - Jakovleva, Tatiana

AU - Feofanova, Natalia

AU - Denisova, Elena

AU - Dubinina, Anastasia

AU - Sitnikova, Natalia

AU - Makarova, Elena

N1 - Copyright: This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2019/12

Y1 - 2019/12

N2 - Fasting is often used for obesity correction but the "refeeding syndrome" limits its efficiency, and molecular mechanisms underlying metabolic response to different food availability are under investigation. Sex was shown to affect hormonal and metabolic reactions to fasting/refeeding. The aim of this study was to evaluate hormonal and transcriptional responses to fasting and refeeding in male and female C57Bl/6J mice. Sex asymmetry was observed both at the hormonal and transcriptional levels. Fasting (24 h) induced increase in hepatic Fgf21 gene expression, which was associated with elevation of plasma FGF21 and adiponectin levels, and the upregulation of expression of hepatic (Pparα, Cpt1α) and muscle (Cpt1β, Ucp3) genes involved in fatty acid oxidation. These changes were more pronounced in females. Refeeding (6 h) evoked hyperinsulinemia and increased hepatic expression of gene related to lipogenesis (Fasn) only in males and hyperleptinemia and increase in Fgf21 gene expression in muscles and adipose tissues only in females. The results suggest that in mice, one of the molecular mechanisms underlying sex asymmetry in hepatic Pparα, Cpt1α, muscle Cpt1β, and Ucp3 expression during fasting is hepatic Fgf21 expression, and the reason for sex asymmetry in hepatic Fasn expression during refeeding is male-specific hyperinsulinemia.

AB - Fasting is often used for obesity correction but the "refeeding syndrome" limits its efficiency, and molecular mechanisms underlying metabolic response to different food availability are under investigation. Sex was shown to affect hormonal and metabolic reactions to fasting/refeeding. The aim of this study was to evaluate hormonal and transcriptional responses to fasting and refeeding in male and female C57Bl/6J mice. Sex asymmetry was observed both at the hormonal and transcriptional levels. Fasting (24 h) induced increase in hepatic Fgf21 gene expression, which was associated with elevation of plasma FGF21 and adiponectin levels, and the upregulation of expression of hepatic (Pparα, Cpt1α) and muscle (Cpt1β, Ucp3) genes involved in fatty acid oxidation. These changes were more pronounced in females. Refeeding (6 h) evoked hyperinsulinemia and increased hepatic expression of gene related to lipogenesis (Fasn) only in males and hyperleptinemia and increase in Fgf21 gene expression in muscles and adipose tissues only in females. The results suggest that in mice, one of the molecular mechanisms underlying sex asymmetry in hepatic Pparα, Cpt1α, muscle Cpt1β, and Ucp3 expression during fasting is hepatic Fgf21 expression, and the reason for sex asymmetry in hepatic Fasn expression during refeeding is male-specific hyperinsulinemia.

KW - sex-specific Fgf21 gene expression

KW - lipid glucose oxidation

KW - fasting refeeding

KW - mice

KW - liver

KW - adipose tissues

KW - muscle

KW - PPAR-ALPHA

KW - GENDER-DIFFERENCE

KW - GENE-EXPRESSION

KW - RECEPTOR-ALPHA

KW - FATTY-ACID

KW - LEPTIN

KW - GAMMA

KW - FIBROBLAST-GROWTH-FACTOR-21

KW - METABOLISM

KW - Adipose tissues

KW - Sex-specific Fgf21 gene expression

KW - Liver

KW - Fasting refeeding

KW - Lipid glucose oxidation

KW - Mice

KW - Muscle

UR - http://www.scopus.com/inward/record.url?scp=85090816323&partnerID=8YFLogxK

U2 - 10.3390/cells8121529

DO - 10.3390/cells8121529

M3 - Article

C2 - 31783664

VL - 8

JO - Cells

JF - Cells

SN - 2073-4409

IS - 12

M1 - 1529

ER -