Dataset Information

Intergenerational transmission of glucose intolerance and obesity by in utero undernutrition in mice.

ABSTRACT:

Objective

Low birth weight (LBW) is associated with increased risk of obesity, diabetes, and cardiovascular disease during adult life. Moreover, this programmed disease risk can progress to subsequent generations. We previously described a mouse model of LBW, produced by maternal caloric undernutrition (UN) during late gestation. LBW offspring (F(1)-UN generation) develop progressive obesity and impaired glucose tolerance (IGT) with aging. We aimed to determine whether such metabolic phenotypes can be transmitted to subsequent generations in an experimental model, even in the absence of altered nutrition during the second pregnancy.

Research design and methods

We intercrossed female and male F(1) adult control (C) and UN mice and characterized metabolic phenotypes in F(2) offspring.

Results

We demonstrate that 1) reduced birth weight progresses to F(2) offspring through the paternal line (Cfemale -Cmale = 1.64 g; Cfemale -UNmale = 1.57 g, P < 0.05; UNfemale -Cmale = 1.64 g; UNfemale -UNmale = 1.60 g, P < 0.05), 2) obesity progresses through the maternal line (percent body fat: Cfemale -Cmale = 22.4%; Cfemale -UNmale = 22.9%; UNfemale -Cmale = 25.9%, P < 0.05; UNfemale -UNmale = 27.5%, P < 0.05), and 3) IGT progresses through both parental lineages (glucose tolerance test area under curve Cfemale -Cmale = 100; Cfemale -UNmale = 122, P < 0.05; UNfemale -Cmale = 131, P < 0.05; UNfemale -UNmale = 151, P < 0.05). Mechanistically, IGT in both F(1) and F(2) generations is linked to impaired beta-cell function, explained, in part, by dysregulation of Sur1 expression.

Conclusions

Maternal undernutrition during pregnancy (F(0)) programs reduced birth weight, IGT, and obesity in both first- and second-generation offspring. Sex-specific transmission of phenotypes implicates complex mechanisms including alterations in the maternal metabolic environment (transmaternal inheritance of obesity), gene expression mediated by developmental and epigenetic pathways (transpaternal inheritance of LBW), or both (IGT).

SUBMITTER: Jimenez-Chillaron JC

PROVIDER: S-EPMC2628621 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Intergenerational transmission of glucose intolerance and obesity by in utero undernutrition in mice.

Jimenez-Chillaron Josep C JC Isganaitis Elvira E Charalambous Marika M Gesta Stephane S Pentinat-Pelegrin Thais T Faucette Ryan R RR Otis Jessica P JP Chow Alice A Diaz Ruben R Ferguson-Smith Anne A Patti Mary-Elizabeth ME

Diabetes 20081118 2

<h4>Objective</h4>Low birth weight (LBW) is associated with increased risk of obesity, diabetes, and cardiovascular disease during adult life. Moreover, this programmed disease risk can progress to subsequent generations. We previously described a mouse model of LBW, produced by maternal caloric undernutrition (UN) during late gestation. LBW offspring (F(1)-UN generation) develop progressive obesity and impaired glucose tolerance (IGT) with aging. We aimed to determine whether such metabolic phe ...[more]

PMID: 19017762

Similar Datasets

Project description:ObjectiveObesity and osteoarthritis (OA) are 2 major public health issues affecting millions of people worldwide. Whereas parental obesity affects the predisposition to diseases such as cancer or diabetes in children, transgenerational influences on musculoskeletal conditions such as OA are poorly understood. This study was undertaken to assess the intergenerational effects of a parental/grandparental high-fat diet on the metabolic and skeletal phenotype, systemic inflammation, and predisposition to OA in 2 generations of offspring in mice.MethodsMetabolic phenotype and predisposition to OA were investigated in the first and second (F1 and F2) generations of offspring (n = 10-16 mice per sex per diet) bred from mice fed a high-fat diet (HFD) or a low-fat control diet. OA was induced by destabilizing the medial meniscus. OA, synovitis, and adipose tissue inflammation were determined histologically, while bone changes were measured using micro-computed tomography. Serum and synovial cytokines were measured by multiplex assay.ResultsParental high-fat feeding showed an intergenerational effect, with inheritance of increased weight gain (up to 19% in the F1 generation and 9% in F2), metabolic imbalance, and injury-induced OA in at least 2 generations of mice, despite the fact that the offspring were fed the low-fat diet. Strikingly, both F1 and F2 female mice showed an increased predisposition to injury-induced OA (48% higher predisposition in F1 and 19% in F2 female mice fed the HFD) and developed bone microarchitectural changes that were attributable to parental and grandparental high-fat feeding.ConclusionThe results of this study reveal a detrimental effect of parental HFD and obesity on the musculoskeletal integrity of 2 generations of offspring, indicating the importance of further investigation of these effects. An improved understanding of the mechanisms involved in the transmissibility of diet-induced changes through multiple generations may help in the development of future therapies that would target the effects of obesity on OA and related conditions.

Dataset Information

Intergenerational transmission of glucose intolerance and obesity by in utero undernutrition in mice.

Objective

Research design and methods

Results

Conclusions

Publications

Intergenerational transmission of glucose intolerance and obesity by in utero undernutrition in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets