Skip to main content Accessibility help

Adipose tissue uncoupling protein 1 levels and function are increased in a mouse model of developmental obesity induced by maternal exposure to high-fat diet

  • E. Bytautiene Prewit (a1), C. Porter (a2), M. La Rosa (a1), N. Bhattarai (a2), H. Yin (a1), P. Gamble (a1), T. Kechichian (a1) and L. S. Sidossis (a2) (a3)...


With brown adipose tissue (BAT) becoming a possible therapeutic target to counteract obesity, the prenatal environment could represent a critical window to modify BAT function and browning of white AT. We investigated if levels of uncoupling protein 1 (UCP1) and UCP1-mediated thermogenesis are altered in offspring exposed to prenatal obesity. Female CD-1 mice were fed a high-fat (HF) or standard-fat (SF) diet for 3 months before breeding. After weaning, all pups were placed on SF. UCP1 mRNA and protein levels were quantified using quantitative real-time PCR and Western blot analysis, respectively, in brown (BAT), subcutaneous (SAT) and visceral (VAT) adipose tissues at 6 months of age. Total and UCP1-dependent mitochondrial respiration were determined by high-resolution respirometry. A Student’s t-test and Mann–Whitney test were used (significance: P<0.05). UCP1 mRNA levels were not different between the HF and SF offspring. UCP1 protein levels, total mitochondrial respiration and UCP1-dependent respiration were significantly higher in BAT from HF males (P=0.02, P=0.04, P=0.005, respectively) and females (P=0.01, P=0.04, P=0.02, respectively). In SAT, the UCP1 protein was significantly lower in HF females (P=0.03), and the UCP1-dependent thermogenesis was significantly lower from HF males (P=0.04). In VAT, UCP1 protein levels and UCP1-dependent respiration were significantly lower only in HF females (P=0.03, P=0.04, respectively). There were no differences in total respiration in SAT and VAT. Prenatal exposure to maternal obesity leads to significant increases in UCP1 levels and function in BAT in offspring with little impact on UCP1 levels and function in SAT and VAT.


Corresponding author

*Address for correspondence: E. Bytautiene Prewit, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, 301 University Blvd, Galveston, TX 77555-1062, USA. E-mail:


Hide All
1. Writing, G, Roger, VL, Go, AS, et al. Executive summary: heart disease and stroke statistics – 2011 update. Circulation. 2011; 123, 459463.
2. Fryar, CD, Hirsch, R, Eberhardt, MS, Yoon, SS, Wright, JD. Hypertension, high serum total cholesterol, and diabetes: racial and ethnic prevalence differences in U.S. adults, 1999-2006. NCHS Data Brief. 2010; 36, 18.
3. American Heart Association. Statistical fact sheet. Women and Cardiovascular Diseases: Statistics, 2006. Retrieved 1 May 2006 from http://wwwamericanheartorg/downloadable/heart/1136818052118Females06pdf.
4. Thom, T, Haase, N, Rosamond, W, et al. Heart disease and stroke statistics – 2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2006; 113, e85e151.
5. Huda, SS, Brodie, LE, Sattar, N. Obesity in pregnancy: prevalence and metabolic consequences. Semin Fetal Neonatal Med. 2010; 15, 7076.
6. Galtier-Dereure, F, Boegner, C, Bringer, J. Obesity and pregnancy: complications and cost. American J Clin Nutr. 2000; 71(5 Suppl.), 1242S1248S.
7. Kim, SY, Dietz, PM, England, L, Morrow, B, Callaghan, WM. Trends in pre-pregnancy obesity in nine states, 1993-2003. Obesity. 2007; 15, 986993.
8. Lu, GC, Rouse, DJ, DuBard, M, et al. The effect of the increasing prevalence of maternal obesity on perinatal morbidity. Am J Obstet Gynecol. 2001; 185, 845849.
9. Catalano, PM, Ehrenberg, HM. The short- and long-term implications of maternal obesity on the mother and her offspring. BJOG. 2006; 113, 11261133.
10. Whitaker, RC. Predicting preschooler obesity at birth: the role of maternal obesity in early pregnancy. Pediatrics. 2004; 114, e29e36.
11. Boney, CM, Verma, A, Tucker, R, Vohr, BR. Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics. 2005; 115, e290e296.
12. Koupil, I, Toivanen, P. Social and early-life determinants of overweight and obesity in 18-year-old Swedish men. Int J Obes. 2008; 32, 7381.
13. Mingrone, G, Manco, M, Valera Mora, ME, et al. Influence of maternal obesity on insulin sensitivity and secretion in offspring. Diabetes Care. 2008; 31, 18721876.
14. Desai, M, Jellyman, JK, Han, G, et al. Maternal obesity and high-fat diet program offspring metabolic syndrome. Am J Obstet Gynecol. 2014; 211, 237.e231237.e237.
15. Forsen, T, Eriksson, JG, Tuomilehto, J, et al. Mother’s weight in pregnancy and coronary heart disease in a cohort of Finnish men: follow up study. BMJ. 1997; 315, 837840.
16. Khan, IY, Dekou, V, Douglas, G, et al. A high-fat diet during rat pregnancy or suckling induces cardiovascular dysfunction in adult offspring. Am J Physiol Regul Integr Comp Physiol. 2005; 288, R127R133.
17. Khan, IY, Taylor, PD, Dekou, V, et al. Gender-linked hypertension in offspring of lard-fed pregnant rats. Hypertension. 2003; 41, 168175.
18. Samuelsson, AM, Matthews, PA, Argenton, M, et al. Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming. Hypertension. 2008; 51, 383392.
19. Oben, JA, Mouralidarane, A, Samuelsson, AM, et al. Maternal obesity during pregnancy and lactation programs the development of offspring non-alcoholic fatty liver disease in mice. J Hepatol. 2010; 52, 913920.
20. Oben, JA, Patel, T, Mouralidarane, A, et al. Maternal obesity programmes offspring development of non-alcoholic fatty pancreas disease. Biochem Biophys Res Commun. 2010; 394, 2428.
21. Suter, MA, Ma, J, Vuguin, PM, et al. In utero exposure to a maternal high-fat diet alters the epigenetic histone code in a murine model. Am J Obstet Gynecol. 2014; 210, 463463.
22. Persichetti, A, Sciuto, R, Rea, S, et al. Prevalence, mass, and glucose-uptake activity of 18F-FDG-detected brown adipose tissue in humans living in a temperate zone of Italy. PLoS One. 2013; 8, e63391.
23. Lo Kinyui, A, Sun, L. Turning WAT into BAT: a review on regulators controlling the browning of white adipocytes. Biosci Rep. 2013; 33, e00065.
24. Fenzl, A, Kiefer, FW. Brown adipose tissue and thermogenesis. Horm Mol Biol Clin Investig. 2014; 19, 2537.
25. Porter, C, Herndon, DN, Bhattarai, N, et al. Severe burn injury induces thermogenically functional mitochondria in murine white adipose tissue. Shock. 2015; 44, 258264.
26. Bytautiene, E, Tamayo, E, Kechichian, T, et al. Prepregnancy obesity and sFlt1-induced preeclampsia in mice: developmental programming model of metabolic syndrome. Am J Obstet Gynecol. 2011; 204, 398.e391398.e398.
27. Porter, C, Hurren, NM, Cotter, MV, et al. Mitochondrial respiratory capacity and coupling control decline with age in human skeletal muscle. Am J Physiol Endocrinol Metab. 2015; 309, E224E232.
28. Cannon, B, Nedergaard, J. Respiratory and thermogenic capacities of cells and mitochondria from brown and white adipose tissue. Methods Mol Biol. 2001; 155, 295303.
29. Cannon, B, Nedergaard, J. Nonshivering thermogenesis and its adequate measurement in metabolic studies. J Exp Biol. 2010; 214, 242253.
30. Cannon, B, Nedergaard, J. Studies of thermogenesis and mitochondrial function in adipose tissues. Methods Mol Biol. 2008; 456, 109121.
31. Cannon, B, Nedergaard, J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004; 84, 277359.
32. Matthias, A, Ohlson, KB, Fredriksson, JM, et al. Thermogenic responses in brown fat cells are fully UCP1-dependent. UCP2 or UCP3 do not substitute for UCP1 in adrenergically or fatty acid-induced thermogenesis. J Biol Chem. 2000; 275, 2507325081.
33. Nedergaard, J, Cannon, B. UCP1 mRNA does not produce heat. Biochim Biophys Acta Mol Cell Biol Lipids. 2013; 1831, 943949.
34. Shabalina, IG, Ost, M, Petrovic, N, et al. Uncoupling protein-1 is not leaky. Biochim Biophys Acta. 2010; 1797, 773784.
35. Shabalina, IG, Petrovic, N, de Jong, JM, et al. UCP1 in brite/beige adipose tissue mitochondria is functionally thermogenic. Cell Rep. 2013; 5, 11961203.
36. Elahi, MM, Cagampang, FR, Mukhtar, D, et al. Long-term maternal high-fat feeding from weaning through pregnancy and lactation predisposes offspring to hypertension, raised plasma lipids and fatty liver in mice. Br J Nutr. 2009; 102, 514519.
37. Watkins, AJ, Lucas, ES, Wilkins, A, Cagampang, FRA, Fleming, TP. Maternal periconceptional and gestational low protein diet affects mouse offspring growth, cardiovascular and adipose phenotype at 1 year of age. PLoS One. 2011; 6, e28745.
38. Ojha, S, Robinson, L, Yazdani, M, Symonds, ME, Budge, H. Brown adipose tissue genes in pericardial adipose tissue of newborn sheep are downregulated by maternal nutrient restriction in late gestation. Pediatr Res. 2013; 74, 246251.
39. Felipe, A, Villarroya, F, Mampel, T. Effects of maternal hypocaloric diet feeding on neonatal rat brown adipose tissue. Biol Neonate. 1988; 53, 105112.
40. Priego, T, Sanchez, J, Garcia, A, Palou, A, Pico, C. Maternal dietary fat affects milk fatty acid profile and impacts on weight gain and thermogenic capacity of suckling rats. Lipids. 2013; 48, 481495.
41. Myers, DA, Hanson, K, Mlynarczyk, M, Kaushal, KM, Ducsay, CA. Long-term hypoxia modulates expression of key genes regulating adipose function in the late-gestation ovine fetus. Am J Physiol Regul Integr Comp Physiol. 2008; 294, R1312R1318.
42. de Almeida, DL, Fabricio, GS, Trombini, AB, et al. Early overfeed-induced obesity leads to brown adipose tissue hypoactivity in rats. Cell Physiol Biochem. 2013; 32, 16211630.
43. Xiao, XQ, Williams, SM, Grayson, BE, et al. Excess weight gain during the early postnatal period is associated with permanent reprogramming of brown adipose tissue adaptive thermogenesis. Endocrinology. 2007; 148, 41504159.
44. Carey Satterfield, M, Dunlap, K, Keisler, D, Bazer, F, Wu, G. Arginine nutrition and fetal brown adipose tissue development in diet-induced obese sheep. Amino Acids. 2012; 43, 15931603.
45. Maurer, AD, Reimer, RA. Maternal consumption of high-prebiotic fibre or -protein diets during pregnancy and lactation differentially influences satiety hormones and expression of genes involved in glucose and lipid metabolism in offspring in rats. Br J Nutr. 2011; 105, 329338.
46. Arias, N, Aguirre, L, Fernandez-Quintela, A, et al. MicroRNAs involved in the browning process of adipocytes. J Physiol Biochem. 2015; 72, 509521.
47. Guller, I, McNaughton, S, Crowley, T, et al. Comparative analysis of microRNA expression in mouse and human brown adipose tissue. BMC Genomics. 2015; 16, 111.
48. Quevedo, S, Roca, P, Pico, C, Palou, A. Sex-associated differences in cold-induced UCP1 synthesis in rodent brown adipose tissue. Pflugers Arch. 1998; 436, 689695.



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed