Analysis of time-dependent adaptations in whole-body energy balance in obesity induced by high-fat diet in rats

Lipids in Health and Disease

Rolando B Ceddia¹  Babak Maghdoori¹  Mandeep P Gaidhu¹  Mandy So¹ 

[1] School of Kinesiology and Health Science - Muscle Health Research Center York University, Toronto, ON, Canada

关键词: adiposity;    food intake;    fat oxidation;    skeletal muscle;    ACC;    leptin;    energy expenditure;    UCP-1;    brown adipose tissue;    Energy efficiency;   

Others  :  1212617
DOI  :  10.1186/1476-511X-10-99

 received in 2011-05-17, accepted in 2011-06-16,  发布年份 2011

【 摘 要 】

Background

High-fat (HF) diet has been extensively used as a model to study metabolic disorders of human obesity in rodents. However, the adaptive whole-body metabolic responses that drive the development of obesity with chronically feeding a HF diet are not fully understood. Therefore, this study investigated the physiological mechanisms by which whole-body energy balance and substrate partitioning are adjusted in the course of HF diet-induced obesity.

Methods

Male Wistar rats were fed ad libitum either a standard or a HF diet for 8 weeks. Food intake (FI) and body weight were monitored daily, while oxygen consumption, respiratory exchange ratio, physical activity, and energy expenditure (EE) were assessed weekly. At week 8, fat mass and lean body mass (LBM), fatty acid oxidation and uncoupling protein-1 (UCP-1) content in brown adipose tissue (BAT), as well as acetyl-CoA carboxylase (ACC) content in liver and epidydimal fat were measured.

Results

Within 1 week of ad libitum HF diet, rats were able to spontaneously reduce FI to precisely match energy intake of control rats, indicating that alterations in dietary energy density were rapidly detected and FI was self-regulated accordingly. Oxygen consumption was higher in HF than controls throughout the study as whole-body fat oxidation also progressively increased. In HF rats, EE initially increased, but then reduced as dark cycle ambulatory activity reached values ~38% lower than controls. No differences in LBM were detected; however, epidydimal, inguinal, and retroperitoneal fat pads were 1.85-, 1.89-, and 2.54-fold larger in HF-fed than control rats, respectively. Plasma leptin was higher in HF rats than controls throughout the study, indicating the induction of leptin resistance by HF diet. At week 8, UCP-1 content and palmitate oxidation in BAT were 3.1- and 1.5-fold higher in HF rats than controls, respectively, while ACC content in liver and epididymal fat was markedly reduced.

Conclusion

The thermogenic response induced by the HF diet was offset by increased energy efficiency and time-dependent reduction in physical activity, favoring fat accumulation. These adaptations were mainly driven by the nutrient composition of the diet, since control and HF animals spontaneously elicited isoenergetic intake.

【 授权许可】

   
2011 So et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】

• [1]Spiegelman BM, Flier JS: Obesity and the regulation of energy balance. Cell 2001, 104:531-543.
• [2]Leibel RL: Single Gene Obesities in Rodents: Possible Relevance to Human Obesity. J Nutr 1997, 127:1908S.
• [3]Chua SC Jr, Chung WK, Wu-Peng XS, Zhang Y, Liu SM, Tartaglia L, Leibel RL: Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor. Science 1996, 271(5251):994-6.
• [4]Aleixandre de Artiñano A, Castro M Miguel: Experimental rat models to study the metabolic syndrome. Br J Nutr 2009, 102(9):1246-53.
• [5]Comuzzie AG, Allison DB: The search for human obesity genes. Science 1998, 280(5368):1374-7.
• [6]Buettner R, Schölmerich J, Bollheimer LC: High-fat diets: modeling the metabolic disorders of human obesity in rodents. Obesity (Silver Spring) 2007, 15(4):798-808.
• [7]Augustine KA, Rossi RM: Rodent mutant models of obesity and their correlations to human obesity. Anat Rec 1999, 257(2):64-72.
• [8]Hariri N, Thibault L: High-fat diet-induced obesity in animal models. Nutr Res Rev 2010, 23(2):270-99.
• [9]Woods SC, Seeley RJ, Rushing PA, D'Alessio D, Tso P: A controlled high-fat diet induces an obese syndrome in rats. J Nutr 2003, 133(4):1081-7.
• [10]Kennedy AR, Pissios P, Otu H, Roberson R, Xue B, Asakura K, Furukawa N, Marino FE, Liu FF, Kahn BB, Libermann TA, Maratos-Flier E: A high-fat, ketogenic diet induces a unique metabolic state in mice. Am J Physiol Endocrinol Metab 2007, 292:E1724-E1739.
• [11]Furnes MW, Zhao CM, Chen D: Development of obesity is associated with increased calories per meal rather than per day. A study of high-fat diet-induced obesity in young rats. Obes Surg 2009, 19(10):1430-8.
• [12]Araujo RL, Andrade BM, Padrón AS, Gaidhu MP, Perry RL, Carvalho DP, Ceddia RB: High-fat diet increases thyrotropin and oxygen consumption without altering circulating 3,5,3'-triiodothyronine (T3) and thyroxine in rats: the role of iodothyronine deiodinases, reverse T3 production, and whole-body fat oxidation. Endocrinology 2010, 151:3460-9.
• [13]Jéquier E, Tappy L: Regulation of body weight in humans. Physiol Rev 1999, 79:451-80.
• [14]Schwartz MW, Woods SC, Seeley RJ, Barsh GS, Baskin DG, Leibel RL: Is the energy homeostasis system inherently biased toward weight gain? Diabetes 2003, 52:232-238.
• [15]McLean JA, Tobin G: Animal and Human Calorimetry. Cambridge Univ. Press; 1987.
• [16]Levin BE, Triscari J, Hogan S, Sullivan AC: Resistance to diet-induced obesity: food intake, pancreatic sympathetic tone, and insulin. Am J Physiol 1987, 252:R471-8.
• [17]Chang S, Graham B, Yakubu F, Lin D, Peters JC, Hill JO: Metabolic differences between obesity-prone and obesity-resistant rats. Am J Physiol 1990, 259:R1103-10.
• [18]Pagliassotti MJ, Knobel SM, Shahrokhi KA, Manzo AM, Hill JO: Time course of adaptation to a high-fat diet in obesity-resistant and obesity-prone rats. Am J Physiol 1994, 267:R659-64.
• [19]Fediuc S, Gaidhu MP, Ceddia RB: Inhibition of insulin-stimulated glycogen synthesis by 5-aminoimidasole-4-carboxamide-1-beta-d-ribofuranoside-induced adenosine 5'-monophosphate-activated protein kinase activation: interactions with Akt, glycogen synthase kinase 3-3alpha/beta, and glycogen synthase in isolated rat soleus muscle. Endocrinology 2006, 147:5170-7.
• [20]Gaidhu MP, Anthony NM, Patel P, Hawke TJ, Ceddia RB: Dysregulation of lipolysis and lipid metabolism in visceral and subcutaneous adipocytes by high-fat diet: role of ATGL, HSL, and AMPK. Am J Physiol Cell Physiol 2010, 298:C961-C971.
• [21]Gaidhu MP, Fediuc S, Ceddia RB: 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside-induced AMP-activated protein kinase phosphorylation inhibits basal and insulin-stimulated glucose uptake, lipid synthesis, and fatty acid oxidation in isolated rat adipocytes. J Biol Chem 2006, 281:25956-64.
• [22]Brozek J, Grande F, Anderson JT, Keys A: Densitometric analysis of body composition: Revision of some quantitative assumptions. Ann N Y Acad Sci 1963, 110:113-40.
• [23]Rosenbaum M, Goldsmith R, Bloomfield D, Magnano A, Weimer L, Heymsfield S, Gallagher D, Mayer L, Murphy E, Leibel RL: Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J Clin Invest 2005, 115:3579-3586.
• [24]Rosenbaum M, Vandenborne K, Goldsmith R, Simoneau JA, Heymsfield S, Joanisse DR, Hirsch J, Murphy E, Matthews D, Segal KR, Leibel RL: Effects of experimental weight perturbation on skeletal muscle work efficiency in human subjects. Am J Physiol Regul Integr Comp Physiol 2003, 285:R183-R192.
• [25]Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI: An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006, 444(7122):1027-31.
• [26]Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI: The effect of diet on human gut microbiome: A metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med 2009, 1(6):14. 6ra
• [27]Novak CM, Levine JA: Central neural and endocrine mechanisms of non-exercise activity thermogenesis and their potential impact on obesity. J Neuroendocrinol 2007, 19:923-40.
• [28]Nogueiras R, López M, Lage R, Perez-Tilve D, Pfluger P, Mendieta-Zerón H, Sakkou M, Wiedmer P, Benoit SC, Datta R, Dong JZ, Culler M, Sleeman M, Vidal-Puig A, Horvath T, Treier M, Diéguez C, Tschöp MH: Bsx, a novel hypothalamic factor linking feeding with locomotor activity, is regulated by energy availability. Endocrinology 2008, 149:3009-3015.
• [29]Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A, Xue B, Mu J, Foufelle F, Ferré P, Birnbaum MJ, Stuck BJ, Kahn BB: AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 2004, 428:569-574.