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Updated: Jul 17, 2026
Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
Maternal protein restriction permanently programs adipocyte growth and development in adult male rat offspring
Ting Zhang1, Haiyan Guan, Edith Arany
1Department of Obstetrics and Gynaecology, Children's Health Research Institute and Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada.
Insights
Maternal protein restriction (MPR) permanently programs adipocyte precursors in male offspring. These cells show increased proliferation and altered growth under reduced serum, indicating lasting effects on fat development.
Area of Science:
- Developmental programming
- Adipogenesis
- Nutritional epigenetics
Background:
- Maternal protein restriction (MPR) during gestation and lactation causes fetal growth restriction and visceral adiposity in male rat offspring.
- Understanding the cellular mechanisms underlying this programming is crucial for addressing metabolic health consequences.
Purpose of the Study:
- To investigate if MPR permanently alters adipocyte precursor (preadipocyte) proliferation and differentiation in adult male rat offspring.
- To determine if MPR-induced changes in preadipocytes are due to inherent cellular abnormalities or persistent in vivo influences.
Main Methods:
- Isolation and in vitro culture of preadipocytes from visceral adipose tissue of control and MPR-exposed adult male rats.
- Assessment of preadipocyte proliferation using [(3)H]-thymidine incorporation.
- Evaluation of differentiation using biochemical and morphological markers.
- Analysis of preadipocyte proliferation in subcultures and under reduced serum conditions.
Main Results:
- MPR significantly increased preadipocyte proliferation by nearly twofold without affecting differentiation rates.
- The heightened proliferation rate persisted in subcultures, suggesting an inherent abnormality in MPR preadipocytes.
- MPR preadipocytes exhibited markedly reduced proliferation under low serum conditions (5% and 2.5% serum).
Conclusions:
- MPR permanently programs adipocyte precursors, leading to excessive proliferation under standard conditions.
- This programming results in altered cellular behavior, with attenuated growth under nutrient-limited environments.
- These findings highlight the lasting impact of early-life nutrition on adipocyte development and potential metabolic disease risk.
Abstract:
We previously demonstrated that maternal protein restriction (MPR) during pregnancy and lactation led to fetal growth restriction and development of increased visceral adiposity in adult male rat offspring. Here we studied the rate of proliferation and differentiation of adipocyte precursors (preadipocytes) in vitro to investigate whether MPR may permanently program adipocyte growth and development in adult male offspring. Preadipocytes were isolated from visceral adipose tissue of control and MPR offspring at 130 days of age, and cultured under standard conditions. The rate of proliferation was studied by [(3)H]-thymidine incorporation, and the rate of differentiation assessed with the use of biochemical and morphological markers. Although it did not affect the rate of differentiation, MPR increased the rate of preadipocyte proliferation by almost twofold. To ascertain if the increased proliferation was due to persisting in vivo influences or aberrations inherent in the precursor cells, we studied the rate of preadipocyte proliferation in subcultures. We found that the increased rate of proliferation of MPR preadipocytes persisted throughout the first two subcultures, indicative of an inherent abnormality. In addition, we examined the rate of preadipocyte proliferation under reduced serum conditions. We showed that MPR reduced the rate of preadipocyte proliferation to 56 and 35% of the control in the presence of 5 and 2.5% serum, respectively. Taken together, these results demonstrate that MPR permanently programs adipocyte growth and development such that adipocyte precursors derived from MPR offspring replicate excessively under standard culture conditions but exhibit markedly attenuated growth rate under reduced serum conditions.
