Fasting triglyceride concentrations are associated with markers of lipid metabolism and glucose homeostasis in healthy, non-obese dogs in lean and overweight condition.
[en] Serum triglyceride concentrations increase in dogs with obesity, which is typically assessed by body condition score (BCS), however little is known about changes that take place in non-obese dogs in overweight condition. Further, the associations of triglyceride levels with other markers of energy homeostasis are poorly characterised in healthy animals. The present study aimed to evaluate associations between both BCS and triglyceride concentrations with other markers of lipid and glucose metabolism in healthy, non-obese dogs, as well as to assess whether these markers change significantly in non-obese dogs with overweight as compared to their lean counterparts. Serum concentrations of cholesterol, free fatty acids, triglycerides, insulin, glucose and fructosamine were measured in 532 healthy, client-owned dogs, assigned either to 'lean' (BCS: 3-5) or 'overweight' (BCS: 6-7) categories. Generalised linear mixed models were used to assess associations between BCS categories, triglyceride concentrations and other variables, correcting for the effect of breed. Compared with lean dogs, overweight dogs had a greater serum cholesterol concentration (95% CI, 5.3-6.2 mmol/L or 205-237 mg/dL versus 5.1-5.4 mmol/L or 198-210 mg/dL, p = 0.0032), insulin concentration (95% CI, 17.5-22.1 μU/ml versus 16.7-18.0 μU/ml, p = 0.0374) and were older (95% CI, 4.0-5.3 versus 3.4-3.7 years, p = 0.0005). Triglyceride concentrations were positively associated with fructosamine (r 2 = 0.31, p = 0.0012), cholesterol (r 2 = 0.25, p < 0.0001), insulin (r 2 = 0.14, p = 0.0030) and glucose (r 2 = 0.10, p = 0.0014) concentrations, and negatively associated with free fatty acid concentrations (r 2 = 0.11, p < 0.0001). However, there was no association between triglyceride concentrations and age. In conclusion, both BCS and triglyceride concentrations were associated with other markers of glucose and lipid metabolism in non-obese healthy dogs, amongst which those with overweight showed metabolic changes as compared to their lean counterparts. Triglyceride concentrations were associated with an increase in insulin and fructosamine concentrations that might reflect an early-phase impairment in glucose tolerance which, surprisingly, was concurrent with lower basal free fatty acid concentrations.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Gomez Fernandez Blanco, Carlos ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH)
Peeters, Dominique ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Médecine vétérinaire comparée
Farnir, Frédéric ; Université de Liège - ULiège > Département de gestion vétérinaire des Ressources Animales (DRA)
Höglund, Katja; Department of Animal Biosciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
Gouni, Vassiliki; INSERM, IMRB, Université Paris-Est Créteil, Créteil, France ; IMRB, École Nationale Vétérinaire d'Alfort, Maisons-Alfort, France
Wiberg, Maria; Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
Lundgren Willesen, Jakob; Department of Veterinary Clinical Sciences, University of Copenhagen, Frederiksberg, Denmark
Hanås, Sofia; Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden ; Evidensia Specialist Animal Hospital Strömsholm, Strömsholm, Sweden
McEntee, Kathleen; Department of Clinical Sciences, College of Veterinary Medicine, University of Liège, Liège, Belgium ; Faculty of Medicine, Université Libre de Bruxelles (ULB), Brussels, Belgium
Tiret, Laurent; INSERM, IMRB, Université Paris-Est Créteil, Créteil, France ; IMRB, École Nationale Vétérinaire d'Alfort, Maisons-Alfort, France
Häggström, Jens; Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
Lohi, Hannes; Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland ; Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland ; Folkhälsan Research Center, Helsinki, Finland
Chetboul, Valérie; INSERM, IMRB, Université Paris-Est Créteil, Créteil, France ; IMRB, École Nationale Vétérinaire d'Alfort, Maisons-Alfort, France
Fredholm, Merete; Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark
Seppälä, Eija; Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland ; Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland ; Folkhälsan Research Center, Helsinki, Finland
Lequarré, Anne-Sophie ; Université de Liège - ULiège > Département de gestion vétérinaire des Ressources Animales (DRA)
German, Alexander James; Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom
Merveille, Anne-Christine ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Médecine vétérinaire comparée
Fasting triglyceride concentrations are associated with markers of lipid metabolism and glucose homeostasis in healthy, non-obese dogs in lean and overweight condition.
AG is an employee of the University of Liverpool, but his post is financially supported by Royal Canin. AG has also received financial remuneration for providing educational material, speaking at conferences, and consultancy work from this company; all such remuneration has been for projects unrelated to the work reported in this manuscript.The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The present study received funding from the European Commission (Grant/Award number: FP7-LUPA, GA-201370).
Ouchi N Parker JL Lugus JJ Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. (2011) 11:85–97. doi: 10.1038/nri2921, PMID: 21252989
Punthakee Z Goldenberg R Katz P. Definition, classification and diagnosis of diabetes, prediabetes and metabolic syndrome. Can J Diabetes. (2018) 42:S10–5. doi: 10.1016/j.jcjd.2017.10.003, PMID: 29650080
Osto M Lutz TA. Translational value of animal models of obesity—focus on dogs and cats. Eur J Pharmacol. (2015) 759:240–52. doi: 10.1016/j.ejphar.2015.03.036
Verkest KR. Is the metabolic syndrome a useful clinical concept in dogs? A review of the evidence. Vet J. (2014) 199:24–30. doi: 10.1016/j.tvjl.2013.09.057, PMID: 24246648
Chandler M Cunningham S Lund EM Khanna C Naramore R Patel A et al. Obesity and associated comorbidities in people and companion animals: a one health perspective. J Comp Pathol. (2017) 156:296–309. doi: 10.1016/j.jcpa.2017.03.006, PMID: 28460795
Weeth LP. Other risks/possible benefits of obesity. Vet Clin North Am Small Anim Pract. (2016) 46:843–53. doi: 10.1016/j.cvsm.2016.04.007
Clark M Hoenig M. Metabolic effects of obesity and its interaction with endocrine diseases. Vet Clin North Am Small Anim Pract. (2016) 46:797–815. doi: 10.1016/j.cvsm.2016.04.004
Kealy RD Lawler DF Ballam JM Mantz SL Biery DN Greeley EH et al. Effects of diet restriction on life span and age-related changes in dogs. J Am Vet Med Assoc. (2002) 220:1315–20. doi: 10.2460/javma.2002.220.1315
Lund EM Armstrong PJ Kirk CA Klausner JS. Prevalence and risk factors for obesity in adult dogs from private US veterinary practices. J Appl Res Vet Med. (2006) 4:177–86.
Endenburg N Soontararak S Charoensuk C Van Lith HA. Quality of life and owner attitude to dog overweight and obesity in Thailand and the Netherlands. BMC Vet Res. (2018) 14:221. doi: 10.1186/S12917-018-1531-Z, PMID: 29986701
Yam PS Butowski CF Chitty JL Naughton G Wiseman-Orr ML Parkin T et al. Impact of canine overweight and obesity on health-related quality of life. Prev Vet Med. (2016) 127:64–9. doi: 10.1016/j.prevetmed.2016.03.013
Muñoz-Garach A Cornejo-Pareja I Tinahones F. Does metabolically healthy obesity exist? Nutrients. (2016) 8:320. doi: 10.3390/nu8060320
Chang Y Jung H-S Yun KE Cho J Ahn J Chung EC et al. Metabolically healthy obesity is associated with an increased risk of diabetes independently of nonalcoholic fatty liver disease. Obesity. (2016) 24:1996–2003. doi: 10.1002/oby.21580, PMID: 27474900
Stefan N Schick F Häring H-U. Causes, characteristics, and consequences of metabolically unhealthy Normal weight in humans. Cell Metab. (2017) 26:292–300. doi: 10.1016/j.cmet.2017.07.008, PMID: 28768170
Tvarijonaviciute A Ceron JJ Holden SL Cuthbertson DJ Biourge V Morris PJ et al. Obesity-related metabolic dysfunction in dogs: a comparison with human metabolic syndrome. BMC Vet Res. (2012) 8:147. doi: 10.1186/1746-6148-8-147
Tvarijonaviciute A Ceron JJ De Torre C Ljubić BB Holden SL Queau Y et al. Obese dogs with and without obesity-related metabolic dysfunction – a proteomic approach. BMC Vet Res. (2016) 12:211. doi: 10.1186/s12917-016-0839-9
Laflamme D. Development and validation of a body condition score system for dogs. Canine Pract. (1997) 22:10–5.
German AJ Holden SL Morris PJ Biourge V. Comparison of a bioimpedance monitor with dual-energy X-ray absorptiometry for noninvasive estimation of percentage body fat in dogs. Am J Vet Res. (2010) 71:393–8. doi: 10.2460/ajvr.71.4.393, PMID: 20367047
Jeusette I Greco D Aquino F Detilleux J Peterson M Romano V et al. Effect of breed on body composition and comparison between various methods to estimate body composition in dogs. Res Vet Sci. (2010) 88:227–32. doi: 10.1016/j.rvsc.2009.07.009, PMID: 19692101
Lequarré AS Andersson L André C Fredholm M Hitte C Leeb T et al. LUPA: a European initiative taking advantage of the canine genome architecture for unravelling complex disorders in both human and dogs. Vet J. (2011) 189:155–9. doi: 10.1016/j.tvjl.2011.06.013, PMID: 21752675
Brooks D Churchill J Fein K Linder D Michel KE Tudor K et al. 2014 AAHA weight management guidelines for dogs and cats. J Am Anim Hosp Assoc. (2014) 50:1–11. doi: 10.5326/JAAHA-MS-6331
Tropf M Nelson OL Lee PM Weng HY. Cardiac and metabolic variables in obese dogs. J Vet Intern Med. (2017) 31:1000–7. doi: 10.1111/jvim.14775, PMID: 28608635
Bailhache E Nguyen P Krempf M Siliart B Magot T Ouguerram K. Lipoproteins Abnormalities In Obese Insulin-Resistant Dogs. Metabolism. (2003) 52:559–64. doi: 10.1053/meta.2003.50110, PMID: 12759884
Gayet C Bailhache E Dumon H Martin L Siliart B Nguyen P. Insulin resistance and changes in plasma concentration of Tnfalpha, IGF1, and NEFA in dogs during weight gain and obesity. J Anim Physiol Anim Nutr. (2004) 88:157–65. doi: 10.1111/j.1439-0396.2003.00473.x
Jeusette IC Lhoest ET Istasse LP Diez MO. Influence of obesity on plasma lipid and lipoprotein concentrations in dogs. Am J Vet Res. (2005) 66:81–6. doi: 10.2460/ajvr.2005.66.81
Tribuddharatana T Kongpiromchean Y Sribhen K Sribhen C. Biochemical alterations and their relationships with the metabolic syndrome components in canine obesity. Kasetsart J - Nat Sci. (2011) 45:622–8.
José Lahm Cardoso M Fagnani R Zaghi Cavalcante C De Souza Zanutto M Júnior AZ Holsback Da Silveira Fertonani L et al. Blood pressure, serum glucose, cholesterol, and triglycerides in dogs with different body scores. Vet Med Int. (2016) 2016:1–7. doi: 10.1155/2016/8675283
Adolphe JL Silver TI Childs H Drew MD Weber LP. Short-term obesity results in detrimental metabolic and cardiovascular changes that may not be reversed with weight loss in an obese dog model. Br J Nutr. (2014) 112:647–56. doi: 10.1017/S0007114514001214, PMID: 24877650
Diez M Michaux C Jeusette I Baldwin P Istasse L Biourge V. Evolution of blood parameters during weight loss in experimental obese beagle dogs. J Anim Physiol Anim Nutr. (2004) 88:166–71. doi: 10.1111/J.1439-0396.2003.00474.X
German AJ Hervera M Hunter L Holden SL Morris PJ Biourge V et al. Improvement in insulin resistance and reduction in plasma inflammatory Adipokines after weight loss in obese dogs. Domest Anim Endocrinol. (2009) 37:214–26. doi: 10.1016/j.domaniend.2009.07.001, PMID: 19674864
Tvarijonaviciute A Tecles F Martinez-Subiela S Ceron JJ. Effect of weight loss on inflammatory biomarkers in obese dogs. Vet J. (2012) 193:570–2. doi: 10.1016/j.tvjl.2012.02.015, PMID: 22464400
Kim SP Catalano KJ Hsu IR Chiu JD Richey JM Bergman RN. Nocturnal free fatty acids are uniquely elevated in the longitudinal development of diet-induced insulin resistance and hyperinsulinemia. Am J Physiol - Endocrinol Metab. (2007) 292:E1590–8. doi: 10.1152/ajpendo.00669.2006
Verkest KR Rand JS Fleeman LM Morton JM. Spontaneously obese dogs exhibit greater postprandial glucose, triglyceride, and insulin concentrations than lean dogs. Domest Anim Endocrinol [Internet]. (2012) 42:103–12. doi: 10.1016/j.domaniend.2011.10.002
Söder J Wernersson S Hagman R Karlsson I Malmlöf K Höglund K. Metabolic and hormonal response to a feed-challenge test in lean and overweight dogs. J Vet Intern Med. (2016) 30:574–82. doi: 10.1111/jvim.13830, PMID: 26822126
Hoenig M. Comparative aspects of human, canine, and feline obesity and factors predicting progression to diabetes. Vet Sci. (2014) 1:121–35. doi: 10.3390/vetsci1020121
Chan JM Rimm EB Colditz GA Stampfer MJ Willett WC. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care. (1994) 17:961–9. doi: 10.2337/diacare.17.9.961, PMID: 7988316
Veiga APM Santos AP Santos WIM FHD G. Fructosamine as a tool on the evaluation of insulin resistant obese dogs. ARC J Anim Vet Sci. (2016) 2:2455–518. doi: 10.20431/2455-2518.0202004
Broussolle C Tricot F Garcia I Orgiazzi J Revol A. Evaluation of the Fructosamine test in obesity: consequences for the assessment of past glycemic control in diabetes. Clin Biochem. (1991) 24:203–9. doi: 10.1016/0009-9120(91)90586-4, PMID: 2040093
Woo J Cockram C Lau E Chan A Swaminathan R. Influence of obesity on plasma Fructosamine concentration. Clin Chem. (1992) 38:2190–2. doi: 10.1093/clinchem/38.11.2190
Zoran DL. Obesity in dogs and cats: a metabolic and endocrine disorder. Vet Clin North Am Small Anim Pract. (2010) 40:221–39. doi: 10.1016/J.Cvsm.2009.10.009
Aronson D Bartha P Zinder O Kerner A Markiewicz W Avizohar O et al. Obesity is the major determinant of elevated C-reactive protein in subjects with the metabolic syndrome. Int J Obes. (2004) 28:674–9. doi: 10.1038/sj.ijo.0802609, PMID: 14993913
Radakovich LB Truelove MP Pannone SC Olver CS Santangelo KS. Clinically healthy overweight and obese dogs differ from lean controls in select CBC and serum biochemistry values. Vet Clin Pathol. (2017) 46:221–6. doi: 10.1111/Vcp.12468, PMID: 28272815
Tvarijonaviciute A Martinez S Gutierrez A Ceron JJ Tecles F. Serum acute phase proteins concentrations in dogs during experimentally short-term induced overweight. a preliminary study. Res Vet Sci. (2011) 90:31–4. doi: 10.1016/j.rvsc.2010.05.008
Veiga APM Price CA De Oliveira ST Dos Santos AP Campos R Barbosa PR et al. Association of canine obesity with reduced serum levels of C-reactive protein. J Vet Diagnostic Investig. (2008) 20:224–8. doi: 10.1177/104063870802000214, PMID: 18319438
Geffré A Concordet D Braun JP Trumel C. Reference value advisor: a new freeware set of macroinstructions to calculate reference intervals with Microsoft excel. Vet Clin Pathol. (2011) 40:107–12. doi: 10.1111/j.1939-165X.2011.00287.x, PMID: 21366659
Friedrichs KR Harr KE Freeman KP Szladovits B Walton RM Barnhart KF et al. ASVCP reference interval guidelines: determination of De novo reference intervals in veterinary species and other related topics. Vet Clin Pathol. (2012) 41:441–53. doi: 10.1111/vcp.12006, PMID: 23240820
R development Core team: A language and environment for statistical computing. Vienna, Austria: R Foundation For Statistical Computing (2014).
National Research Council Of The National Academies. Guide for the care and use of laboratory animals. Washington, DC: National Academy Press (2001).
German AJ Holden SL Bissot T Morris PJ Biourge V. Use of starting condition score to estimate changes in body weight and composition during weight loss in obese dogs. Res Vet Sci. (2009) 87:249–54. doi: 10.1016/j.rvsc.2009.02.007
Peña C Suárez L Bautista I Montoya JA Juste MC. Relationship between analytic values and canine obesity. J Anim Physiol Anim Nutr. (2008) 92:324–5. doi: 10.1111/J.1439-0396.2007.00786.X, PMID: 18477313
Bailhache E Ouguerram K Gayet C Krempf M Siliart B Magot T et al. An insulin-resistant Hypertriglyceridaemic normotensive obese dog model: assessment of insulin resistance by the Euglycaemic Hyperinsulinaemic clamp in combination with the stable isotope technique. J Anim Physiol Anim Nutr. (2003) 87:86–95. doi: 10.1046/J.1439-0396.2003.00419.X, PMID: 14511132
Jeusette IC Detilleux J Shibata H Saito M Honjoh T Delobel A et al. Effects of chronic obesity and weight loss on plasma ghrelin and leptin concentrations in dogs. Res Vet Sci. (2005) 79:169–75. doi: 10.1016/j.rvsc.2004.11.012, PMID: 15924935
Lee S Kweon O-K Kim WH. Increased leptin and leptin receptor expression in dogs with gallbladder Mucocele. J Vet Intern Med. (2017) 31:36–42. doi: 10.1111/jvim.14612, PMID: 28032399
Parker VJ Freeman LM. Association between body condition and survival in dogs with acquired chronic kidney disease. J Vet Intern Med. (2011) 25:1306–11. doi: 10.1111/J.1939-1676.2011.00805.X, PMID: 22092621
Kahn SE Hull RL Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. (2006) 444:840–6. doi: 10.1038/nature05482
Mattheeuws D Rottiers R Kaneko JJ Vermeulen A. Diabetes mellitus in dogs: relationship of obesity to glucose tolerance and insulin response. Am J Vet Res. (1984) 45:98–103.
Ader M Stefanovski D Kim SP Richey JM Ionut V Catalano KJ et al. Hepatic insulin clearance is the primary determinant of insulin sensitivity in the Normal dog. Obesity. (2014) 22:1238–45. doi: 10.1002/oby.20625
Verkest KR Fleeman LM Rand JS Morton JM. Evaluation of Beta-cell sensitivity to glucose and first-phase insulin secretion in obese dogs. Am J Vet Res. (2011) 72:357–66. doi: 10.2460/ajvr.72.3.357
Verkest KR Fleeman LM Morton JM Ishioka K Rand JS. Compensation for obesity-induced insulin resistance in dogs: assessment of the effects of leptin, adiponectin, and glucagon-like Peptide-1 using path analysis. Domest Anim Endocrinol. (2011) 41:24–34. doi: 10.1016/j.domaniend.2011.02.001
Verkest KR Fleeman LM Morton JM Groen SJ Suchodolski JS Steiner JM et al. Association of postprandial serum triglyceride concentration and serum canine pancreatic lipase Immunoreactivity in overweight and obese dogs. J Vet Intern Med. (2012) 26:46–53. doi: 10.1111/j.1939-1676.2011.00844.x, PMID: 22233344
Lawler DF Larson BT Ballam JM Smith GK Biery DN Evans RH et al. Diet restriction and ageing in the dog: major observations over two decades. Br J Nutr. (2008) 99:793–805. doi: 10.1017/S0007114507871686
Kim SP Ellmerer M Kirkman EL Bergman RN. Β-cell “rest” accompanies reduced first-pass hepatic insulin extraction in the insulin-resistant, fat-fed canine model. Am J Physiol - Endocrinol Metab. (2007) 292:E1581–9. doi: 10.1152/ajpendo.00351.2006
Eckel N Mühlenbruch K Meidtner K Boeing H Stefan N Schulze MB. Characterization of metabolically unhealthy Normal-weight individuals: risk factors and their associations with type 2 diabetes. Metabolism. (2015) 64:862–71. doi: 10.1016/j.metabol.2015.03.009, PMID: 25861921
Cambuli VM Musiu MC Incani M Paderi M Serpe R Marras V et al. Assessment of adiponectin and leptin as biomarkers of positive metabolic outcomes after lifestyle intervention in overweight and obese children. J Clin Endocrinol Metab. (2008) 93:3051–7. doi: 10.1210/jc.2008-0476, PMID: 18492759
Peng YF Wei YS. The relationships between serum Fructosamine concentrations and lipid profiles in community-dwelling adults. Sci Rep. (2017) 7:3–7. doi: 10.1038/s41598-017-07287-5
Ginsberg HN Zhang Y-L Hernandez-Ono A. Regulation of plasma triglycerides in insulin resistance and diabetes. Arch Med Res. (2005) 36:232–40. doi: 10.1016/j.arcmed.2005.01.005
Glueck CJ Khan NA Umar M Uppal MS Ahmed W Morrison JA et al. Insulin resistance and triglycerides. J Investig Med. (2009) 57:874–81. doi: 10.2310/JIM.0b013e3181bca9d2
Hoffman RP. Increased fasting triglyceride levels are associated with hepatic insulin resistance in Caucasian but not African-American adolescents. Diabetes Care. (2006) 29:1402–4. doi: 10.2337/dc06-2460, PMID: 16732033
Kashyap S Belfort R Gastaldelli A Pratipanawatr T Berria R Pratipanawatr W et al. A sustained increase in plasma free fatty acids impairs insulin secretion in nondiabetic subjects genetically predisposed to develop type 2 diabetes. Diabetes. (2003) 52:2461–74. doi: 10.2337/diabetes.52.10.2461, PMID: 14514628
Kim SP Ellmerer M Van Citters GM Bergman RN. Primacy of hepatic insulin 622 resistance in the development of the metabolic syndrome induced by an isocaloric 623 moderate-fat diet in the dog. Diabetes [Internet]. (2003) Oct [cited 2016 Aug 52:2453–60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14514627
Leclerc L Thorin C Flanagan J Biourge V Serisier S Nguyen P. Higher neonatal growth rate and body condition score at 7 months are predictive factors of obesity in adult female beagle dogs. BMC Vet Res. (2017) 13:1–13. doi: 10.1186/s12917-017-0994-7
German AJ Holden SL Moxham GL Holmes KL Hackett RM Rawlings JM. A simple, reliable tool for owners to assess the body condition of their dog or cat. J Nutr. (2006) 136:2031S–3S. doi: 10.1093/jn/136.7.2031S
