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Programmed upregulation of adipogenic transcription factors in intrauterine growth-restricted offspring.

ABSTRACT: As enhanced adipogenesis contributes to programmed obesity, adipogenic and lipogenic signaling pathways in intrauterine growth restricted (IUGR) offspring were examined. From 10 days to term gestation, rats received ad libitum food (control) or were 50% food-restricted (IUGR). Pups were nursed and weaned to ad libitum diet. mRNA and protein levels of adipogenic transcription factors and lipid enzymes (1 day and 9 month) and adipocyte cell size (3 weeks and 9 months) were determined. One day-old IUGR males showed upregulation of peroxisome proliferator-activated receptor (PPAR gamma(2)), including upstream factors regulating PPAR gamma, and RXR alpha, with which PPAR gamma heterodimerizes. Intracellular lipolytic enzyme (hormone-sensitive lipase) was downregulated. Nine-month-old IUGR males showed upregulation of adipogenic and lipogenic (SREBP1c) transcription factors with upregulation of enzymes facilitating fatty acid uptake (lipoprotein lipase) and synthesis (fatty acid synthase), leading to hypertrophic adipocytes. Paradoxical upregulation of adipogenesis signaling cascade prior to the development of obesity in IUGR males suggests early changes in signaling mechanisms.

SUBMITTER: Desai M

PROVIDER: S-EPMC3444244 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Programmed upregulation of adipogenic transcription factors in intrauterine growth-restricted offspring.

Desai Mina M Guang Han Ferelli Monica M Kallichanda Natash N Lane Robert H RH

Reproductive sciences (Thousand Oaks, Calif.) 20081001 8

As enhanced adipogenesis contributes to programmed obesity, adipogenic and lipogenic signaling pathways in intrauterine growth restricted (IUGR) offspring were examined. From 10 days to term gestation, rats received ad libitum food (control) or were 50% food-restricted (IUGR). Pups were nursed and weaned to ad libitum diet. mRNA and protein levels of adipogenic transcription factors and lipid enzymes (1 day and 9 month) and adipocyte cell size (3 weeks and 9 months) were determined. One day-old ...[more]

PMID: 19017816

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Project description:OBJECTIVE:The objective of this study was to investigate the effects of dietary choline supplementation on hepatic lipid metabolism and gene expression in finishing pigs with intrauterine growth retardation (IUGR). METHODS:Using a 2×2 factorial design, eight normal birth weight (NBW) and eight IUGR weaned pigs were fed either a basal diet (NBW pigs fed a basal diet, NC; IUGR pigs fed a basal diet, IC) or a diet supplemented with two times more choline than the basal diet (NBW pigs fed a high-choline diet, NH; IUGR pigs fed a high-choline diet, IH) until 200 d of age. RESULTS:The results showed that the IUGR pigs had reduced body weight compared with the NBW pigs (p<0.05 from birth to d 120; p = 0.07 from d 120 to 200). Increased (p<0.05) free fatty acid (FFA) and triglyceride levels were observed in the IUGR pigs compared with the NBW pigs. Choline supplementation decreased (p<0.05) the levels of FFAs and triglycerides in the serum of the pigs. The activities of malate dehydrogenase and glucose 6-phosphate dehydrogenase were both increased (p<0.05) in the livers of the IUGR pigs. Choline supplementation decreased (p<0.05) malate dehydrogenase activity in the liver of the pigs. Gene expression of fatty acid synthase (FAS) was higher (p<0.05) in the IC group than in the other groups, and choline supplementation decreased (p<0.05) FAS and acetyl-CoA carboxylase ? expression in the livers of the IUGR pigs. The expression of carnitine palmitoyl transferase 1A (CPT1A) was lower (p<0.05) in the IC group than in the other groups, and choline supplementation increased (p<0.05) the expression of CPT1A in the liver of the IUGR pigs and decreased (p<0.01) the expression of hormone-sensitive lipase in both types of pigs. The gene expression of phosphatidylethanolamine N-methyltransferase (PEMT) was higher (p<0.05) in the IC group than in the other groups, and choline supplementation significantly reduced (p<0.05) PEMT expression in the liver of the IUGR pigs. CONCLUSION:In conclusion, the lipid metabolism was abnormal in IUGR pigs, but the IUGR pigs consuming twice the normal level of choline had improved circulating lipid parameters, which could be related to the decreased activity of nicotinamide adenine dinucleotide phosphate-generating enzymes or the altered expressions of lipid metabolism-related genes.

Project description:Epidemiological studies report an inverse association between birth weight and risk for kidney disease that may differ between males and females, but studies investigating this association are limited. This study tested the hypothesis that male intrauterine growth-restricted offspring in a model of low birth weight induced by placental insufficiency in the rat exhibit enhanced renal injury in response to a persistent secondary renal insult while female growth-restricted offspring are protected. For this study, control offspring from sham-operated dams and growth-restricted offspring from reduced uterine perfusion dams underwent uninephrectomy or a sham procedure at 18 months of age. One month later, urinary markers of renal injury, renal function, and histological damage were measured. Results were analyzed using 2-way ANOVA. Male and female offspring were assessed separately. Proteinuria and urinary neutrophil gelatinase-associated lipocalin were significantly elevated in male growth-restricted offspring exposed to uninephrectomy when compared to male uninephrectomized control. Urinary kidney injury marker-1 was elevated in male uninephrectomized growth-restricted offspring relative to male sham growth-restricted but not to male uninephrectomized controls. Likewise, urinary neutrophil gelatinase-associated lipocalin was elevated in female uninephrectomized growth-restricted offspring but only when compared to female sham growth-restricted offspring. Markers of renal function including glomerular filtration rate and serum creatinine were impaired after uninephrectomy in female offspring regardless of birth weight. Histological parameters did not differ between control and growth-restricted offspring. Collectively, these studies suggest that both male and female growth-restricted offspring demonstrate susceptibility to renal injury following uninephrectomy; however, only male growth-restricted offspring exhibited an increase in renal markers of injury in response to uninephrectomy relative to same-sex control counterparts. These findings further suggest that urinary excretion of protein, kidney injury marker-1, and neutrophil gelatinase-associated lipocalin may be early markers of kidney injury in growth-restricted offspring exposed to a secondary renal insult such as reduction in renal mass.

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Programmed upregulation of adipogenic transcription factors in intrauterine growth-restricted offspring.

Publications

Programmed upregulation of adipogenic transcription factors in intrauterine growth-restricted offspring.

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