期刊
ENDOCRINOLOGY
卷 151, 期 4, 页码 1570-1580出版社
ENDOCRINE SOC
DOI: 10.1210/en.2009-1133
关键词
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资金
- Clinical Nutrition Research Unit Center [1P30 DK072476]
- National Institute of Diabetes and Digestive and Kidney Diseases
- American Diabetes Association [1-09-JF-51]
- Pennington Biomedical Research Foundation
- [DK073189]
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK072476, R01DK073189] Funding Source: NIH RePORTER
The mechanisms linking intrauterine growth retardation (IUGR) with adulthood obesity and diabetes are unclear. These studies investigated energy homeostasis in 8- and 20-wk-old male and female mice subjected to protein deficiency in utero. Pregnant C57BL/6J female mice were fed a protein-deficient diet (6% protein). Undernourished offspring (UO) and controls (CO) were cross-fostered to lactating dams fed a 20% control diet. The 24-h profiles of energy expenditure, feeding behavior, physical activity, and whole-body substrate preference was assessed using 8-wk UO and CO weaned onto control diet. Blood chemistries, glucose tolerance, and expression of genes involved in hepatic lipid and glucose metabolism were analyzed in 8- and 20-wk-old CO and UO fed control or a high-fat diet. UO exhibited IUGR with catch-up growth at 8 wk of age and increased severity of diet-induced obesity and insulin resistance by 20 wk of age. Therefore, fetal malnutrition in the C57BL/6J mouse increases sensitivity to diet-induced obesity. Abnormal daily rhythms in food intake and metabolism, increased lipogenesis, and inflammation preceded obesity in the UO group. Arrhythmic expression of circadian oscillator genes was evident in brain, liver, and muscle of UO at 8 and 20 wk of age. Expression of the clock-associated nuclear receptor and transcription repressor Rev-erb alpha was reduced in liver and muscle of UO. Altered circadian physiology may be symptomatic of the metabolic dysregulation associated with IUGR, and altered feeding behavior and substrate metabolism may contribute to the obese phenotype. (Endocrinology 151: 1570-1580, 2010)
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