Impaired oxidative capacity due to decreased CPT1b levels as a contributing factor to fat accumulation in obesity

American Journal of Physiology - Regulatory Integrative and Comparative Physiology

Volumn 308, Issue 11, 2015, Pages R973-R982

  Ratner, Cecilia ^a,b   Madsen, Andreas Nygaard ^a,b   Kristensen, Line Vildbrad ^a,b   Skov, Louise Julie ^a,b   Pedersen, Katrine Seide ^c   Mortensen, Ole Hartvig ^c   Knudsen, Gitte Moos ^d   Raun, Kirsten ^e   Holst, Birgitte ^a,b  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b Capital Region   (Denmark)

^c Department of Biomedical Sciences Cellular and Metabolic Research Section   (Denmark)

^d University of Copenhagen   (Denmark)

^e NOVO NORDISK A S   (Denmark)

Author keywords

Adipose tissue; Ghrelin; Indirect calorimetry; Polygenic obese; Respiratory exchange ratio

Indexed keywords

ACYL COENZYME A DESATURASE; CARNITINE PALMITOYLTRANSFERASE; CARNITINE PALMITOYLTRANSFERASE IB; GHRELIN; UNCLASSIFIED DRUG; CPT1B PROTEIN, RAT; INSULIN; LEPTIN;

ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BODY COMPOSITION; CALORIMETRY; CONTROLLED STUDY; ENERGY EXPENDITURE; INTRAABDOMINAL FAT; LIPID OXIDATION; LIPID STORAGE; LUNG GAS EXCHANGE; MALE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; OBESITY; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; SUBCUTANEOUS FAT; WESTERN DIET; WHITE ADIPOSE TISSUE; ANIMAL; BLOOD; DISEASE MODEL; DOWN REGULATION; DRUG EFFECTS; EATING; ENERGY METABOLISM; ENZYMOLOGY; GENE EXPRESSION REGULATION; GENETICS; HYPOTHALAMUS; LIPID DIET; METABOLISM; OXIDATION REDUCTION REACTION; PATHOPHYSIOLOGY; SKELETAL MUSCLE; TIME; WEIGHT GAIN;

ADIPOSITY; ANIMALS; CALORIMETRY, INDIRECT; CARNITINE O-PALMITOYLTRANSFERASE; DIET, HIGH-FAT; DISEASE MODELS, ANIMAL; DOWN-REGULATION; EATING; ENERGY METABOLISM; GENE EXPRESSION REGULATION; GHRELIN; HYPOTHALAMUS; INSULIN; INTRA-ABDOMINAL FAT; LEPTIN; MAGNETIC RESONANCE IMAGING; MALE; MUSCLE, SKELETAL; OBESITY; OXIDATION-REDUCTION; RATS; SUBCUTANEOUS FAT; TIME FACTORS; WEIGHT GAIN;

EID: 84930885231     PISSN: 03636119     EISSN: 15221490     Source Type: Journal    
DOI: 10.1152/ajpregu.00219.2014     Document Type: Article

References (58)

1. Abizaid A, Liu ZW, Andrews ZB, Shanabrough M, Borok E, Elsworth JD, Roth RH, Sleeman MW, Picciotto MR, Tschop MH, Gao XB, Horvath TL. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. J Clin Invest 116: 3229–3239, 2006.
2. Andrews ZB, Liu ZW, Walllingford N, Erion DM, Borok E, Friedman JM, Tschop MH, Shanabrough M, Cline G, Shulman GI, Coppola A, Gao XB, Horvath TL, Diano S. UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals. Nature 454: 846–851, 2008.
3. Astrup A, Raben A, Buemann B, Toubro S. Fat metabolism in the predisposition to obesity. Ann NY Acad Sci 827: 417–430, 1997.
4. Bjursell M, Gerdin AK, Lelliott CJ, Egecioglu E, Elmgren A, Tornell J, Oscarsson J, Bohlooly YM. Acutely reduced locomotor activity is a major contributor to Western diet-induced obesity in mice. Am J Physiol Endocrinol Metab 294: E251–E260, 2008.
5. Briggs DI, Enriori PJ, Lemus MB, Cowley MA, Andrews ZB. Dietinduced obesity causes ghrelin resistance in arcuate NPY/AgRP neurons. Endocrinology 151: 4745–4755, 2010.
6. Briggs DI, Lockie SH, Benzler J, Wu Q, Stark R, Reichenbach A, Hoy AJ, Lemus MB, Coleman HA, Parkington HC, Tups A, Andrews ZB. Evidence that diet-induced hyperleptinemia, but not hypothalamic gliosis, causes ghrelin resistance in NPY/AgRP neurons of male mice. Endocrinology 155: 2411–2422, 2014.
7. Brownlow BS, Petro A, Feinglos MN, Surwit RS. The role of motor activity in diet-induced obesity in C57BL/6J mice. Physiol Behav 60: 37–41, 1996.
8. Clegg DJ, Benoit SC, Reed JA, Woods SC, Dunn-Meynell A, Levin BE. Reduced anorexic effects of insulin in obesity-prone rats fed a moderate-fat diet. Am J Physiol Regul Integr Comp Physiol 288: R981–R986, 2005.
9. Cowley MA, Smith RG, Diano S, Tschop M, Pronchuk N, Grove KL, Strasburger CJ, Bidlingmaier M, Esterman M, Heiman ML, Garcia- Segura LM, Nillni EA, Mendez P, Low MJ, Sotonyi P, Friedman JM, Liu H, Pinto S, Colmers WF, Cone RD, Horvath TL. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37: 649–661, 2003.
10. Despres JP. Health consequences of visceral obesity. Ann Med 33: 534–541, 2001.
11. Druce MR, Wren AM, Park AJ, Milton JE, Patterson M, Frost G, Ghatei MA, Small C, Bloom SR. Ghrelin increases food intake in obese as well as lean subjects. Int J Obes (Lond) 29: 1130–1136, 2005.
12. Duca FA, Sakar Y, Covasa M. Combination of obesity and high-fat feeding diminishes sensitivity to GLP-1R agonist exendin-4. Diabetes 62: 2410–2415, 2013.
13. Ellis AC, Hyatt TC, Hunter GR, Gower BA. Respiratory quotient predicts fat mass gain in premenopausal women. Obesity 18: 2255–2259, 2010.
14. Gardiner JV, Campbell D, Patterson M, Kent A, Ghatei MA, Bloom SR, Bewick GA. The hyperphagic effect of ghrelin is inhibited in mice by a diet high in fat. Gastroenterology 138: 2468–2476, 2476 e2461, 2010.
15. Guidotti S, Meijer HA, van Dijk G. Validity of the doubly labeled water method for estimating CO2 production in mice under different nutritional conditions. Am J Physiol Endocrinol Metab 305: E317–E324, 2013.
16. Hainer V, Kunesova M, Parizkova J, Stich V, Mikulova R, Slaba S. Respiratory quotient in obesity: its association with an ability to retain weight loss and with parental obesity. Prague Med Rep 101: 99–104, 2000.
17. Holst B, Madsen KL, Jansen AM, Jin C, Rickhag M, Lund VK, Jensen M, Bhatia V, Sorensen G, Madsen AN, Xue Z, Moller SK, Woldbye D, Qvortrup K, Huganir R, Stamou D, Kjaerulff O, Gether U. PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance. PLoS Biol 11: e1001542, 2013.
18. Horvath TL, Sarman B, Garcia-Caceres C, Enriori PJ, Sotonyi P, Shanabrough M, Borok E, Argente J, Chowen JA, Perez-Tilve D, Pfluger PT, Bronneke HS, Levin BE, Diano S, Cowley MA, Tschop MH. Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity. Proc Natl Acad Sci USA 107: 14875–14880, 2010.
19. Huda MS, Dovey T, Wong SP, English PJ, Halford J, McCulloch P, Cleator J, Martin B, Cashen J, Hayden K, Wilding JP, Pinkney J. Ghrelin restores ‘lean-type’ hunger and energy expenditure profiles in morbidly obese subjects but has no effect on postgastrectomy subjects. Int J Obes 33: 317–325, 2009.
20. Hulver MW, Berggren JR, Carper MJ, Miyazaki M, Ntambi JM, Hoffman EP, Thyfault JP, Stevens R, Dohm GL, Houmard JA, Muoio DM. Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans. Cell Metab 2: 251–261, 2005.
21. Irani BG, Dunn-Meynell AA, Levin BE. Altered hypothalamic leptin, insulin, and melanocortin binding associated with moderate-fat diet and predisposition to obesity. Endocrinology 148: 310–316, 2007.
22. Irani BG, Le Foll C, Dunn-Meynell AA, Levin BE. Ventromedial nucleus neurons are less sensitive to leptin excitation in rats bred to develop diet-induced obesity. Am J Physiol Regul Integr Comp Physiol 296: R521–R527, 2009.
23. Iwakura H, Akamizu T, Ariyasu H, Irako T, Hosoda K, Nakao K, Kangawa K. Effects of ghrelin administration on decreased growth hormone status in obese animals. Am J Physiol Endocrinol Metab 293: E819–E825, 2007.
24. Jackman MR, Kramer RE, MacLean PS, Bessesen DH. Trafficking of dietary fat in obesity-prone and obesity-resistant rats. Am J Physiol Endocrinol Metab 291: E1083–E1091, 2006.
25. Jackman MR, MacLean PS, Bessesen DH. Energy expenditure in obesity-prone and obesity-resistant rats before and after the introduction of a high-fat diet. Am J Physiol Regul Integr Comp Physiol 299: R1097–R1105, 2010.
26. Ji H, Friedman MI. Reduced capacity for fatty acid oxidation in rats with inherited susceptibility to diet-induced obesity. Metabolism 56: 1124–1130, 2007.
27. Kamegai J, Tamura H, Shimizu T, Ishii S, Sugihara H, Wakabayashi I. Chronic central infusion of ghrelin increases hypothalamic neuropeptide Y and Agouti-related protein mRNA levels and body weight in rats. Diabetes 50: 2438–2443, 2001.
28. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402: 656–660, 1999.
29. Levin BE. Arcuate NPY neurons and energy homeostasis in diet-induced obese and resistant rats. Am J Physiol Regul Integr Comp Physiol 276: R382–R387, 1999.
30. Levin BE. Spontaneous motor activity during the development and maintenance of diet-induced obesity in the rat. Physiol Behav 50: 573–581, 1991.
31. Levin BE, Dunn-Meynell AA, Balkan B, Keesey RE. Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats. Am J Physiol Regul Integr Comp Physiol 273: R725–R730, 1997.
32. Levin BE, Dunn-Meynell AA, Banks WA. Obesity-prone rats have normal blood-brain barrier transport but defective central leptin signaling before obesity onset. Am J Physiol Regul Integr Comp Physiol 286: R143–R150, 2004.
33. Levin BE, Dunn-Meynell AA, Ricci MR, Cummings DE. Abnormalities of leptin and ghrelin regulation in obesity-prone juvenile rats. Am J Physiol Endocrinol Metab 285: E949–E957, 2003.
34. Levin BE, Sullivan AC. Glucose-induced sympathetic activation in obesity- prone and resistant rats. Int J Obes (Lond) 13: 235–246, 1989.
35. Lutz TA, Woods SC. Overview of animal models of obesity. Curr Protoc Pharmacol Chapter 5: Unit5 61, 2012.
36. Madsen AN, Hansen G, Paulsen SJ, Lykkegaard K, Tang-Christensen M, Hansen HS, Levin BE, Larsen PJ, Knudsen LB, Fosgerau K, Vrang N. Long-term characterization of the diet-induced obese and diet-resistant rat model: a polygenetic rat model mimicking the human obesity syndrome. J Endocrinol 206: 287–296, 2010.
37. Marra M, Scalfi L, Contaldo F, Pasanisi F. Fasting respiratory quotient as a predictor of long-term weight changes in non-obese women. Ann Nutr Metab 48: 189–192, 2004.
38. Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, Matsukura S. A role for ghrelin in the central regulation of feeding. Nature 409: 194–198, 2001.
39. Novak CM, Kotz CM, Levine JA. Central orexin sensitivity, physical activity, and obesity in diet-induced obese and diet-resistant rats. Am J Physiol Endocrinol Metab 290: E396–E403, 2006.
40. Panchal SK, Brown L. Rodent models for metabolic syndrome research. J Biomed Biotechnol 2011: 351982, 2011.
41. Perez-Leighton CE, Boland K, Teske JA, Billington C, Kotz CM. Behavioral responses to orexin, orexin receptor gene expression, and spontaneous physical activity contribute to individual sensitivity to obesity. Am J Physiol Endocrinol Metab 303: E865–E874, 2012.
42. Perez-Tilve D, Heppner K, Kirchner H, Lockie SH, Woods SC, Smiley DL, Tschop M, Pfluger P. Ghrelin-induced adiposity is independent of orexigenic effects. FASEB J 25: 2814–2822, 2011.
43. Perreault M, Istrate N, Wang L, Nichols AJ, Tozzo E, Stricker- Krongrad A. Resistance to the orexigenic effect of ghrelin in dietaryinduced obesity in mice: reversal upon weight loss. Int J Obes Relat Metab Disord 28: 879–885, 2004.
44. Petersen PS, Jin C, Madsen AN, Rasmussen M, Kuhre R, Egerod KL, Nielsen LB, Schwartz TW, Holst B. Deficiency of the GPR39 receptor is associated with obesity and altered adipocyte metabolism. FASEB J 25: 3803–3814, 2011.
45. Ratner C, Ettrup A, Bueter M, Haahr ME, Compan V, le Roux CW, Levin B, Hansen HH, Knudsen GM. Cerebral markers of the serotonergic system in rat models of obesity and after Roux-en-Y gastric bypass. Obesity 20: 2133–2141, 2012.
46. Seidell JC, Muller DC, Sorkin JD, Andres R. Fasting respiratory exchange ratio and resting metabolic rate as predictors of weight gain: the Baltimore Longitudinal Study on Aging. Int J Obes Relat Metab Disord 16: 667–674, 1992.
47. Shintani M, Ogawa Y, Ebihara K, Aizawa-Abe M, Miyanaga F, Takaya K, Hayashi T, Inoue G, Hosoda K, Kojima M, Kangawa K, Nakao K. Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes 50: 227–232, 2001.
48. Simoneau JA, Veerkamp JH, Turcotte LP, Kelley DE. Markers of capacity to utilize fatty acids in human skeletal muscle: relation to insulin resistance and obesity and effects of weight loss. FASEB J 13: 2051–2060, 1999.
49. So M, Gaidhu MP, Maghdoori B, Ceddia RB. Analysis of timedependent adaptations in whole-body energy balance in obesity induced by high-fat diet in rats. Lipids Health Dis 10: 99, 2011.
50. Tang-Christensen M, Vrang N, Ortmann S, Bidlingmaier M, Horvath TL, Tschop M. Central administration of ghrelin and agouti-related protein (83–132) increases food intake and decreases spontaneous locomotor activity in rats. Endocrinology 145: 4645–4652, 2004.
51. Teske JA, Levine AS, Kuskowski M, Levine JA, Kotz CM. Elevated hypothalamic orexin signaling, sensitivity to orexin A, and spontaneous physical activity in obesity-resistant rats. Am J Physiol Regul Integr Comp Physiol 291: R889–R899, 2006.
52. Theander-Carrillo C, Wiedmer P, Cettour-Rose P, Nogueiras R, Perez-Tilve D, Pfluger P, Castaneda TR, Muzzin P, Schurmann A, Szanto I, Tschop MH, Rohner-Jeanrenaud F. Ghrelin action in the brain controls adipocyte metabolism. J Clin Invest 116: 1983–1993, 2006.
53. Tschop M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 407: 908–913, 2000.
54. Tschop MH, Speakman JR, Arch JR, Auwerx J, Bruning JC, Chan L, Eckel RH, Farese RV Jr, Galgani JE, Hambly C, Herman MA, Horvath TL, Kahn BB, Kozma SC, Maratos-Flier E, Muller TD, Munzberg H, Pfluger PT, Plum L, Reitman ML, Rahmouni K, Shulman GI, Thomas G, Kahn CR, Ravussin E. A guide to analysis of mouse energy metabolism. Nat Methods 9: 57–63, 2012.
55. Wakil SJ, Abu-Elheiga LA. Fatty acid metabolism: target for metabolic syndrome. J Lipid Res 50, Suppl: S138–S143, 2009.
56. Warensjo E, Ohrvall M, Vessby B. Fatty acid composition and estimated desaturase activities are associated with obesity and lifestyle variables in men and women. Nutr Metab Cardiovasc Dis 16: 128–136, 2006.
57. Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, Kennedy AR, Roberts GH, Morgan DG, Ghatei MA, Bloom SR. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 141: 4325–4328, 2000.
58. Zurlo F, Lillioja S, Esposito-Del Puente A, Nyomba BL, Raz I, Saad MF, Swinburn BA, Knowler WC, Bogardus C, and Ravussin E. Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24-h RQ. Am J Physiol Endocrinol Metab 259: E650–E657, 1990.