Effect of Food Restriction and Leptin Supplementation on Fetal Programming in Mice

Pennington, Kathleen A.; Harper, Jennifer L.; Sigafoos, Ashley N.; Beffa, Lindsey M.; Carleton, Stephanie M.; Phillips, Charlotte L.; Schulz, Laura C.

doi:10.1210/en.2012-1119

Cited by 29 publications

(38 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Females were returned to individual cages, and at d1.5, randomly assigned to one of two treatment groups: (1) ad libitum fed plus saline injection (control) or (2) food restricted to 50% of prior consumption levels plus saline injection (restricted). Saline injections were given to permit comparisons to our previous studies, in which we examined placentas at d11.5 and offspring during adulthood using the same two treatment groups (Pennington et al 2012, Schulz et al 2012). In those studies, saline injections were used to control for leptin injections given to a third treatment group, which was not included in this study.…”

Section: Methodsmentioning

confidence: 99%

“…Similar placental adaptations were observed by others in mice restricted through gestational day 16 (Sferruzzi-Perri et al 2011). However, food restriction from d1.5–11.5 had only modest effects on mouse offspring (Pennington et al 2012). As adults, their body weights, glucose tolerance, and response to a high fat diet were not different than those of offspring from control pregnancies.…”

Section: Introductionmentioning

confidence: 99%

“…As adults, their body weights, glucose tolerance, and response to a high fat diet were not different than those of offspring from control pregnancies. Among males only, offspring of food restricted mothers had slightly lower adiposity and greater bone strength than offspring of controls, and increases in Igf1r mRNA and 18s rRNA levels in the liver (Pennington et al 2012). …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Placental changes caused by food restriction during early pregnancy in mice are reversible

et al. 2015

View full text Add to dashboard Cite

In a previous study, 50% calorie restriction in mice from d1.5 to 11.5 of pregnancy resulted in reduced placental weights and areas, relativel sparing of labyrinth zone area compared to junctional zone area, and dramatic changes in global gene expression profiles. However, little lasting effect was seen on adult offspring of these pregnancies, with a slight reduction in adiposity in males and some changes in liver gene expression in both sexes. The goals of the present study were to determine whether the placental changes induced by caloric restriction in early pregnancy had permanent, irreversible effects on the placenta, and whether the changes in liver gene expression in adult offspring were present before birth. There were no differences in placental weights or areas, or the areas of individual placental zones near term in mice that had previously been food restricted. Global gene expression profiles at d18.5 were indistinguishable in placentas from control and previously food-restricted mothers. In fetuses from restricted dams at d18.5, liver expression of Gck, a key regulator of glycogen synthesis, was reduced, whereas its expression was increased in livers from adult offspring of restricted dams. Ppara expression was also reduced in fetal livers from restricted dams at d18.5, but not in adult offspring livers. We conclude that alterations in the placenta caused by nutrient restriction in early pregnancy are reversible, and that alterations in gene expression in livers of adult offspring are not a result of changes initiated during pregnancy and maintained through adulthood.Reproduction (2015) 150 165-172

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Placental changes caused by food restriction during early pregnancy in mice are reversible

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Suggestive evidence comes from epidemiologic cohort studies, which report correlations between weight at birth and 1 y of age with bone integrity later in life (7,8). In animal models, gestational nutrition and hormone concentrations affect skeletal microarchitecture, bone mineral content, strength, growth plate morphology, and osteoblast differentiation capability (9)(10)(11)(12)(13)(14). However, the mechanisms remain unknown.…”

mentioning

confidence: 99%

Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta

Oestreich

Kamp

McCray

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

During fetal development, the uterine environment can have effects on offspring bone architecture and integrity that persist into adulthood; however, the biochemical and molecular mechanisms remain unknown. Myostatin is a negative regulator of muscle mass. Parental myostatin deficiency (Mstn tm1Sjl/+ ) increases muscle mass in wild-type offspring, suggesting an intrauterine programming effect. Here, we hypothesized that Mstn tm1Sjl/+ dams would also confer increased bone strength. In wild-type offspring, maternal myostatin deficiency altered fetal growth and calvarial collagen content of newborn mice and conferred a lasting impact on bone geometry and biomechanical integrity of offspring at 4 mo of age, the age of peak bone mass. Second, we sought to apply maternal myostatin deficiency to a mouse model with osteogenesis imperfecta (Col1a2 oim ), a heritable connective tissue disorder caused by abnormalities in the structure and/or synthesis of type I collagen. Femora of male Col1a2 oim/+ offspring from natural mating of Mstn tm1Sjl/+ dams to Col1a2 oim/+ sires had a 15% increase in torsional ultimate strength, a 29% increase in tensile strength, and a 24% increase in energy to failure compared with age, sex, and genotype-matched offspring from natural mating of Col1a2 oim/+ dams to Col1a2 oim/+ sires. Finally, increased bone biomechanical strength of Col1a2 oim/+ offspring that had been transferred into Mstn tm1Sjl/+ dams as blastocysts demonstrated that the effects of maternal myostatin deficiency were conferred by the postimplantation environment. Thus, targeting the gestational environment, and specifically prenatal myostatin pathways, provides a potential therapeutic window and an approach for treating osteogenesis imperfecta.osteogenesis imperfecta | developmental origins of health and disease | fetal programming | myostatin | bone health O steogenesis imperfecta (OI) is a genetically and clinically heterogeneous heritable connective tissue disorder characterized by anomalies in type I collagen-containing tissues, particularly bone. Clinical manifestations include osteopenia/osteoporosis, fractures, skeletal deformities, short stature, and skeletal muscle weakness. Current therapies entail use of antiresorptive drugs and surgical interventions but have limited success (1). New approaches that decrease fracture risk while minimizing long-term damage to bone integrity are greatly needed. Myostatin, or growth and differentiation factor 8 (GDF8), is a TGF-β family member and negative regulator of muscle growth and development. It is highly conserved across species, primarily expressed in muscle cells, and participates in paracrine and endocrine signaling (2). Recently, we and others have shown that inhibiting myostatin, either genetically or pharmacologically, increases muscle mass and improves bone microarchitecture (3) and mechanical strength (4) in the OI murine (Col1a2 oim ) model. In addition to regulating muscle growth postnatally, myostatin deficiency in the maternal environment increases muscle mass in ...

show abstract

“…Leptin infusion in food-restricted mice during early and midpregnancy promoted development of diet-induced obesity (DIO) in adult female offspring (36); however, the administration of leptin to both protein-restricted and adequately fed rats during the third trimester and lactation protected offspring from obesity induced by high-fat feeding (43,44). However, in the latter experiments, the rats received leptin during both pregnancy and lactation.…”

mentioning

confidence: 99%

Influence of abnormally high leptin levels during pregnancy on metabolic phenotypes in progeny mice

Макарова

Chepeleva

Panchenko

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Makarova EN, Chepeleva EV, Panchenko PE, Bazhan NM. Influence of abnormally high leptin levels during pregnancy on metabolic phenotypes in progeny mice. Am J Physiol Regul Integr Comp Physiol 305: R1268 -R1280, 2013. First published October 2, 2013; doi:10.1152/ajpregu.00162.2013.-Maternal obesity increases the risk of obesity in offspring, and obesity is accompanied by an increase in blood leptin levels. The "yellow" mutation at the mouse agouti locus (A y ) increases blood leptin levels in C57BL preobese pregnant mice without affecting other metabolic characteristics. We investigated the influence of the A y mutation or leptin injection at the end of pregnancy in C57BL mice on metabolic phenotypes and the susceptibility to diet-induced obesity (DIO) in offspring. In both C57BL-A y and leptin-treated mice, the maternal effect was more pronounced in male offspring. Compared with males born to control mothers, males born to A y mothers displayed equal food intake (FI) but decreased body weight (BW) gain after weaning, equal glucose tolerance, and enhanced FI-to-BW ratios on the standard diet but the same FI and BW on the high-fat diet. Males born to A y mothers were less responsive to the anorectic effect of exogenous leptin and less resistant to fasting (were not hyperphagic and gained less weight during refeeding after food deprivation) compared with males born to control mothers. However, all progeny displayed equal hypothalamic expression of Agouti gene-related protein (AgRP), neuropeptide Y (NPY), and proopiomelanocortin (POMC) and equal plasma leptin and glucose levels after food deprivation. Leptin injections in C57BL mice on day 17 of pregnancy decreased BW in both male and female offspring but inhibited FI and DIO only in male offspring. Our results show that hyperleptinemia during pregnancy has sex-specific long-term effects on energy balance regulation in progeny and does not predispose offspring to developing obesity. leptin; pregnancy; developmental programming; mice; high-fat diet BECAUSE OF THE OBESITY EPIDEMIC, the influence of intrauterine and early postnatal conditions on the metabolic phenotypes of individuals later in life has gained increasing attention. Experimental and clinical investigations have shown that maternal obesity during pregnancy increases the risk of the offspring developing obesity (29,39,42). Obesity is characterized by elevated levels of leptin in both nonpregnant and pregnant females (23,30,33). The adipocyte cytokine leptin plays a key role in energy homeostasis regulation (22), and circulating leptin levels are proportional to the body adipose mass (13).A considerable number of studies have identified leptin as a potential programming factor (48). In experimental animal models, expression of the leptin receptor has been detected in various fetal tissues, including cartilage, bone, lung, brain (16), and pancreas (18). Leptin has been shown to activate the differentiation and proliferation of fetal chondrocytes, osteoblasts (2), and islet cells (18) and to promote the migra...

show abstract

Effect of Food Restriction and Leptin Supplementation on Fetal Programming in Mice

Cited by 29 publications

References 50 publications

Placental changes caused by food restriction during early pregnancy in mice are reversible

Placental changes caused by food restriction during early pregnancy in mice are reversible

Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta

Influence of abnormally high leptin levels during pregnancy on metabolic phenotypes in progeny mice

Contact Info

Product

Resources

About