TY - JOUR
T1 - Maternal obesity has sex-dependent effects on insulin, glucose and lipid metabolism and the liver transcriptome in young adult rat offspring
AU - Lomas-Soria, Consuelo
AU - Reyes-Castro, Luis A.
AU - Rodríguez-González, Guadalupe L.
AU - Ibáñez, Carlos A.
AU - Bautista, Claudia J.
AU - Cox, Laura A.
AU - Nathanielsz, Peter W.
AU - Zambrano, Elena
N1 - Funding Information:
This work was supported by the Newton Fund RCUK-CONACyT (Research Councils UK – Consejo Nacional de Ciencia y Tecnología) with the project entitled ‘Interventions to improve maternal metabolic profile and prevent cardio-metabolic and behavioural deficits in future generations due to programming by maternal obesity’. FONCICYT/49/2016. C.L.S., L.A.R., G.L.R.G., C.A.I., C.J.B. and L.A.C. researched data. L.A.C.: acquisition and analysis of RNA-seq data work. P.W.N. and E.Z. were responsible for the study design. C.L.S., P.W.N. and E.Z.: preparation and review of manuscript. All authors have read and approved the final version of this manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed. This work was supported by the Newton Fund RCUK-CONACyT (Research Councils UK – Consejo Nacional de Ciencia y Tecnología) with the project entitled ‘Interventions to improve maternal metabolic profile and prevent cardio-metabolic and behavioural deficits in future generations due to programming by maternal obesity’. FONCICYT/49/2016. We are grateful to Dr Georgina Hernández-Montes from Universidad Nacional Autónoma de México for her technical advice. C.A.I. is a graduate student from Doctorado en Ciencias Bioquímicas, Universidad Nacional Autónoma de México, and is the recipient of a CONACyT fellowship (262656).
Funding Information:
This work was supported by the Newton Fund RCUK-CONACyT (Research Councils UK – Consejo Nacional de Ciencia y Tecnología) with the project entitled ‘Interventions to improve maternal metabolic profile and prevent cardio-metabolic and behavioural deficits in future generations due to programming by maternal obesity’. FONCICYT/49/2016.
Publisher Copyright:
© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society
PY - 2018/10/1
Y1 - 2018/10/1
N2 - Key points: Maternal high-fat diet consumption predisposes to metabolic dysfunction in male and female offspring at young adulthood. Maternal obesity programs non-alcoholic fatty liver disease (NAFLD) in a sex-dependent manner. We demonstrate sex-dependent liver transcriptome profiles in rat offspring of obese mothers. In this study, we focused on pathways related to insulin, glucose and lipid signalling. These results improve understanding of the mechanisms by which a maternal high-fat diet affects the offspring. Abstract: Maternal obesity (MO) predisposes offspring (F1) to obesity, insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD). MO's effects on the F1 liver transcriptome are poorly understood. We used RNA-seq to determine the liver transcriptome of male and female F1 of MO and control-fed mothers. We hypothesized that MO-F1 are predisposed to sex-dependent adult liver dysfunction. Female Wistar rat mothers ate a control (C) or obesogenic (MO) diet from the time they were weaned through breeding at postnatal day (PND) 120, delivery and lactation. After weaning, all male and female F1 ate a control diet. At PND 110, F1 serum, liver and fat were collected to analyse metabolites, histology and liver differentially expressed genes. Male and female MO-F1 showed increased adiposity index, triglycerides, insulin and homeostatic model assessment vs. C-F1 with similar body weight and glucose serum concentrations. MO-F1 males presented greater physiological and histological NAFLD characteristics than MO-F1 females. RNA-seq revealed 1365 genes significantly changed in male MO-F1 liver and only 70 genes in female MO-F1 compared with controls. GO and KEGG analysis identified differentially expressed genes related to metabolic processes. Male MO-F1 liver showed the following altered pathways: insulin signalling (22 genes), phospholipase D signalling (14 genes), NAFLD (13 genes) and glycolysis/gluconeogenesis (7 genes). In contrast, few genes were altered in these pathways in MO-F1 females. In summary, MO programs sex-dependent F1 changes in insulin, glucose and lipid signalling pathways, leading to liver dysfunction and insulin resistance.
AB - Key points: Maternal high-fat diet consumption predisposes to metabolic dysfunction in male and female offspring at young adulthood. Maternal obesity programs non-alcoholic fatty liver disease (NAFLD) in a sex-dependent manner. We demonstrate sex-dependent liver transcriptome profiles in rat offspring of obese mothers. In this study, we focused on pathways related to insulin, glucose and lipid signalling. These results improve understanding of the mechanisms by which a maternal high-fat diet affects the offspring. Abstract: Maternal obesity (MO) predisposes offspring (F1) to obesity, insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD). MO's effects on the F1 liver transcriptome are poorly understood. We used RNA-seq to determine the liver transcriptome of male and female F1 of MO and control-fed mothers. We hypothesized that MO-F1 are predisposed to sex-dependent adult liver dysfunction. Female Wistar rat mothers ate a control (C) or obesogenic (MO) diet from the time they were weaned through breeding at postnatal day (PND) 120, delivery and lactation. After weaning, all male and female F1 ate a control diet. At PND 110, F1 serum, liver and fat were collected to analyse metabolites, histology and liver differentially expressed genes. Male and female MO-F1 showed increased adiposity index, triglycerides, insulin and homeostatic model assessment vs. C-F1 with similar body weight and glucose serum concentrations. MO-F1 males presented greater physiological and histological NAFLD characteristics than MO-F1 females. RNA-seq revealed 1365 genes significantly changed in male MO-F1 liver and only 70 genes in female MO-F1 compared with controls. GO and KEGG analysis identified differentially expressed genes related to metabolic processes. Male MO-F1 liver showed the following altered pathways: insulin signalling (22 genes), phospholipase D signalling (14 genes), NAFLD (13 genes) and glycolysis/gluconeogenesis (7 genes). In contrast, few genes were altered in these pathways in MO-F1 females. In summary, MO programs sex-dependent F1 changes in insulin, glucose and lipid signalling pathways, leading to liver dysfunction and insulin resistance.
KW - Non-alcoholic fatty liver disease
KW - Programming by maternal obesity
KW - RNA seq
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U2 - 10.1113/JP276372
DO - 10.1113/JP276372
M3 - Article
C2 - 29972240
AN - SCOPUS:85052796647
VL - 596
SP - 4611
EP - 4628
JO - Journal of Physiology
JF - Journal of Physiology
SN - 0022-3751
IS - 19
ER -