Relationship of skeletal muscle inflammation with obesity and obesity-associated hyperinsulinemia in horses.
Abstract: Local (skeletal muscle and adipose) and systemic inflammation are implicated in the development of obesity-associated insulin resistance in humans. In horses, obesity is neither strongly nor consistently associated with systemic inflammation. The role of skeletal muscle inflammation in the development of insulin dysregulation (insulin resistance or hyperinsulinemia) remains to be determined. We hypothesized that skeletal muscle inflammation is related to obesity-associated hyperinsulinemia in horses. Thirty-five light-breed horses with body condition scores (BCSs) of 3/9 to 9/9 were studied, including 7 obese, normoinsulinemic (BCS ≥ 7, resting serum insulin < 30 μIU/mL) and 6 obese, hyperinsulinemic (resting serum insulin ≥ 30 μIU/mL) horses. Inflammatory biomarkers were evaluated in skeletal muscle biopsies and plasma. Relationships between markers of inflammation and BCS were evaluated. To assess the role of inflammation in obesity-associated hyperinsulinemia, markers of inflammation were compared among lean or ideal, normoinsulinemic (L-NI); obese, normoinsulinemic (O-NI); and obese, hyperinsulinemic (O-HI) horses. Skeletal muscle and plasma tumor necrosis factor alpha (TNFα) concentrations were negatively correlated with BCS. When comparing inflammatory markers among groups, skeletal muscle TNFα was lower in the O-HI group than in the O-NI or L-NI groups. In horses, neither skeletal muscle nor systemic inflammation appears to be positively related to obesity or obesity-associated hyperinsulinemia. L’inflammation locale (muscle squelettique et tissu adipeux) et systémique sont impliquées dans le développement de la résistance à l’insuline associée à l’obésité chez l’humain. Chez les chevaux, l’obésité n’est pas fortement ou de manière constante associée avec l’inflammation systémique. Le rôle de l’inflammation des muscles squelettiques dans le développement de la dérégulation de l’insuline (résistance à l’insuline ou hyper-insulinémie) reste à être déterminé. Nous avons émis l’hypothèse que chez les chevaux l’inflammation des muscles squelettiques est reliée à l’hyper-insulinémie associée à l’obésité. Trente-cinq chevaux de race légère avec des pointages de condition corporelle (PCCs) variant de 3/9 à 9/9 ont été étudiés, incluant sept chevaux obèses, normo-insulinémique (PCC ≥ 7, insuline sérique au repos < 30 μUI/mL) et six chevaux obèses, hyper-insulinémique (insuline sérique au repos ≥ 30 μUI/mL). Les biomarqueurs de l’inflammation ont été évalués dans des biopsies de muscles squelettiques et le plasma. Les relations entre les marqueurs de l’inflammation et le PCC ont été évaluées. Pour apprécier le rôle de l’inflammation dans l’hyper-insulinémie associée à l’obésité, les marqueurs de l’inflammation ont été comparés parmi les chevaux élancés ou idéal, normo-insulinémique (L-NI); les chevaux obèses, normo-insulinémique (O-NI); et les chevaux obèses, hyperinsulinémique (O-HI). Les concentrations du facteur nécrosant des tumeurs alpha (TNFα) étaient corrélées négativement avec le PCC. Lors de la comparaison des marqueurs de l’inflammation entre les groupes, la concentration de TNFα dans les muscles squelettiques était plus basse dans le groupe O-HI que dans les groupes O-NI ou L-NI. Chez les chevaux, ni l’inflammation systémique ou celle des muscles squelettiques ne semblent reliées positivement à l’obésité ou à l’hyper-insulinémie associée à l’obésité.(Traduit par Docteur Serge Messier).
Publication Date: 2016-07-14 PubMed ID: 27408335PubMed Central: PMC4924556
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research article investigates the relationship between skeletal muscle inflammation and obesity-associated hyperinsulinemia in horses. Findings suggest that neither skeletal muscle nor systemic inflammation appear to be positively correlated with obesity or obesity-associated hyperinsulinemia in horses.
Study Overview and Hypothesis
- The study examined thirty-five light-breed horses with body condition scores (BCSs) ranging from 3/9 to 9/9. This sample included seven obese, normoinsulinemic horses (with BCS ≥ 7 and resting serum insulin < 30 μUI/mL) and six obese, hyperinsulinemic horses (with resting serum insulin ≥ 30 μIU/mL).
- The study hypothesized that skeletal muscle inflammation is linked to obesity-associated hyperinsulinemia in horses.
Methods and Measurements
- Inflammatory biomarkers were evaluated using skeletal muscle biopsies and plasma samples from the horses.
- Researchers then assessed the relationships between these inflammation markers and the Body Conditioning Scores of the horses.
- The role of inflammation in obesity-associated hyperinsulinemia was studied by comparing inflammation markers among lean or ideal, normoinsulinemic (L-NI); obese, normoinsulinemic (O-NI); and obese, hyperinsulinemic (O-HI) horses.
Findings
- Skeletal muscle and plasma concentrations of a substance called tumor necrosis factor alpha (TNFα) were found to be negatively correlated with the BCS. This means that higher BCSs (indicating more fat accumulation) were associated with lower levels of TNFα in the muscle and plasma.
- When comparing inflammation markers among the groups, skeletal muscle TNFα was found to be lower in the O-HI group than in the O-NI or L-NI groups. This implies that horses with obesity-associated hyperinsulinemia had lower levels of muscle inflammation as compared to normal or lean horses.
Conclusions
- From these findings, it appears that neither skeletal muscle inflammation nor systemic inflammation are positively related to obesity or obesity-associated hyperinsulinemia in horses.
- This contradicts the team’s initial hypothesis that suggested a clear connection between skeletal muscle inflammation and obesity-associated hyperinsulinemia.
Cite This Article
APA
Banse HE, Holbrook TC, Frank N, McFarlane D.
(2016).
Relationship of skeletal muscle inflammation with obesity and obesity-associated hyperinsulinemia in horses.
Can J Vet Res, 80(3), 217-224.
Publication
Researcher Affiliations
- Department of Physiological Sciences (Banse, McFarlane) and Department of Veterinary Clinical Sciences (Holbrook), Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma 74078, USA; Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts 01536, USA (Frank).
- Department of Physiological Sciences (Banse, McFarlane) and Department of Veterinary Clinical Sciences (Holbrook), Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma 74078, USA; Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts 01536, USA (Frank).
- Department of Physiological Sciences (Banse, McFarlane) and Department of Veterinary Clinical Sciences (Holbrook), Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma 74078, USA; Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts 01536, USA (Frank).
- Department of Physiological Sciences (Banse, McFarlane) and Department of Veterinary Clinical Sciences (Holbrook), Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma 74078, USA; Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts 01536, USA (Frank).
MeSH Terms
- Animals
- Biomarkers
- Female
- Gene Expression Regulation
- Horse Diseases / etiology
- Horses
- Hyperinsulinism / complications
- Hyperinsulinism / veterinary
- Inflammation / complications
- Inflammation / veterinary
- Insulin / metabolism
- Male
- Muscle, Skeletal / pathology
- Muscular Diseases / complications
- Muscular Diseases / veterinary
- Obesity / complications
- Obesity / veterinary
References
This article includes 43 references
- Tantiwong P, Shanmugasundaram K, Monroy A, Ghosh S, Li M, DeFronzo RA, Cersosimo E, Sriwijitkamol A, Mohan S, Musi N. NF-κB activity in muscle from obese and type 2 diabetic subjects under basal and exercise-stimulated conditions.. Am J Physiol Endocrinol Metab 2010 Nov;299(5):E794-801.
- Plomgaard P, Nielsen AR, Fischer CP, Mortensen OH, Broholm C, Penkowa M, Krogh-Madsen R, Erikstrup C, Lindegaard B, Petersen AM, Taudorf S, Pedersen BK. Associations between insulin resistance and TNF-alpha in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes.. Diabetologia 2007 Dec;50(12):2562-71.
- Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B. Recent advances in the relationship between obesity, inflammation, and insulin resistance.. Eur Cytokine Netw 2006 Mar;17(1):4-12.
- Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic role of white adipose tissue.. Br J Nutr 2004 Sep;92(3):347-55.
- Yang RZ, Lee MJ, Hu H, Pollin TI, Ryan AS, Nicklas BJ, Snitker S, Horenstein RB, Hull K, Goldberg NH, Goldberg AP, Shuldiner AR, Fried SK, Gong DW. Acute-phase serum amyloid A: an inflammatory adipokine and potential link between obesity and its metabolic complications.. PLoS Med 2006 Jun;3(6):e287.
- Park HS, Park JY, Yu R. Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-alpha and IL-6.. Diabetes Res Clin Pract 2005 Jul;69(1):29-35.
- Calabro P, Chang DW, Willerson JT, Yeh ET. Release of C-reactive protein in response to inflammatory cytokines by human adipocytes: linking obesity to vascular inflammation.. J Am Coll Cardiol 2005 Sep 20;46(6):1112-3.
- Anty R, Bekri S, Luciani N, Saint-Paul MC, Dahman M, Iannelli A, Amor IB, Staccini-Myx A, Huet PM, Gugenheim J, Sadoul JL, Le Marchand-Brustel Y, Tran A, Gual P. The inflammatory C-reactive protein is increased in both liver and adipose tissue in severely obese patients independently from metabolic syndrome, Type 2 diabetes, and NASH.. Am J Gastroenterol 2006 Aug;101(8):1824-33.
- Guilherme A, Virbasius JV, Puri V, Czech MP. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes.. Nat Rev Mol Cell Biol 2008 May;9(5):367-77.
- Yudkin JS, Kumari M, Humphries SE, Mohamed-Ali V. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link?. Atherosclerosis 2000 Feb;148(2):209-14.
- Trayhurn P, Drevon CA, Eckel J. Secreted proteins from adipose tissue and skeletal muscle - adipokines, myokines and adipose/muscle cross-talk.. Arch Physiol Biochem 2011 May;117(2):47-56.
- Daoussis D, Antonopoulos I, Yiannopoulos G, Andonopoulos AP. ACTH as first line treatment for acute calcium pyrophosphate crystal arthritis in 14 hospitalized patients.. Joint Bone Spine 2014 Jan;81(1):98-100.
- Ritter J, Kerr LD, Valeriano-Marcet J, Spiera H. ACTH revisited: effective treatment for acute crystal induced synovitis in patients with multiple medical problems.. J Rheumatol 1994 Apr;21(4):696-9.
- Levine T. Treating refractory dermatomyositis or polymyositis with adrenocorticotropic hormone gel: a retrospective case series.. Drug Des Devel Ther 2012;6:133-9.
- Getting SJ, Christian HC, Flower RJ, Perretti M. Activation of melanocortin type 3 receptor as a molecular mechanism for adrenocorticotropic hormone efficacy in gouty arthritis.. Arthritis Rheum 2002 Oct;46(10):2765-75.
- Beech J, Boston RC, McFarlane D, Lindborg S. Evaluation of plasma ACTH, alpha-melanocyte-stimulating hormone, and insulin concentrations during various photoperiods in clinically normal horses and ponies and those with pituitary pars intermedia dysfunction.. J Am Vet Med Assoc 2009 Sep 15;235(6):715-22.
- Mc Gowan TW, Pinchbeck GP, Mc Gowan CM. Evaluation of basal plasma α-melanocyte-stimulating hormone and adrenocorticotrophic hormone concentrations for the diagnosis of pituitary pars intermedia dysfunction from a population of aged horses.. Equine Vet J 2013 Jan;45(1):66-73.
- Adams AA, Katepalli MP, Kohler K, Reedy SE, Stilz JP, Vick MM, Fitzgerald BP, Lawrence LM, Horohov DW. Effect of body condition, body weight and adiposity on inflammatory cytokine responses in old horses.. Vet Immunol Immunopathol 2009 Feb 15;127(3-4):286-94.
- Vick MM, Adams AA, Murphy BA, Sessions DR, Horohov DW, Cook RF, Shelton BJ, Fitzgerald BP. Relationships among inflammatory cytokines, obesity, and insulin sensitivity in the horse.. J Anim Sci 2007 May;85(5):1144-55.
- Treiber K, Carter R, Gay L, Williams C, Geor R. Inflammatory and redox status of ponies with a history of pasture-associated laminitis.. Vet Immunol Immunopathol 2009 Jun 15;129(3-4):216-20.
- Bamford NJ, Potter SJ, Harris PA, Bailey SR. Effect of increased adiposity on insulin sensitivity and adipokine concentrations in horses and ponies fed a high fat diet, with or without a once daily high glycaemic meal.. Equine Vet J 2016 May;48(3):368-73.
- Holbrook TC, Tipton T, McFarlane D. Neutrophil and cytokine dysregulation in hyperinsulinemic obese horses.. Vet Immunol Immunopathol 2012 Jan 15;145(1-2):283-9.
- Suagee JK, Corl BA, Crisman MV, Pleasant RS, Thatcher CD, Geor RJ. Relationships between body condition score and plasma inflammatory cytokines, insulin, and lipids in a mixed population of light-breed horses.. J Vet Intern Med 2013 Jan-Feb;27(1):157-63.
- Tadros EM, Frank N, Donnell RL. Effects of equine metabolic syndrome on inflammatory responses of horses to intravenous lipopolysaccharide infusion.. Am J Vet Res 2013 Jul;74(7):1010-9.
- Burns TA, Geor RJ, Mudge MC, McCutcheon LJ, Hinchcliff KW, Belknap JK. Proinflammatory cytokine and chemokine gene expression profiles in subcutaneous and visceral adipose tissue depots of insulin-resistant and insulin-sensitive light breed horses.. J Vet Intern Med 2010 Jul-Aug;24(4):932-9.
- Waller AP, Huettner L, Kohler K, Lacombe VA. Novel link between inflammation and impaired glucose transport during equine insulin resistance.. Vet Immunol Immunopathol 2012 Oct 15;149(3-4):208-15.
- Lewis MR, Callas PW, Jenny NS, Tracy RP. Longitudinal stability of coagulation, fibrinolysis, and inflammation factors in stored plasma samples.. Thromb Haemost 2001 Dec;86(6):1495-500.
- Andreasson A, Kiss NB, Juhlin CC, Höög A. Long-term storage of endocrine tissues at - 80°C does not adversely affect RNA quality or overall histomorphology.. Biopreserv Biobank 2013 Dec;11(6):366-70.
- Freestone JF, Wolfsheimer KJ, Kamerling SG, Church G, Hamra J, Bagwell C. Exercise induced hormonal and metabolic changes in Thoroughbred horses: effects of conditioning and acepromazine.. Equine Vet J 1991 May;23(3):219-23.
- Perkins GA, Lamb S, Erb HN, Schanbacher B, Nydam DV, Divers TJ. Plasma adrenocorticotropin (ACTH) concentrations and clinical response in horses treated for equine Cushing's disease with cyproheptadine or pergolide.. Equine Vet J 2002 Nov;34(7):679-85.
- Pollock PJ, Prendergast M, Schumacher J, Bellenger CR. Effects of surgery on the acute phase response in clinically normal and diseased horses.. Vet Rec 2005 Apr 23;156(17):538-42.
- Saghizadeh M, Ong JM, Garvey WT, Henry RR, Kern PA. The expression of TNF alpha by human muscle. Relationship to insulin resistance.. J Clin Invest 1996 Feb 15;97(4):1111-6.
- Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance.. J Clin Invest 1995 May;95(5):2409-15.
- Spranger J, Kroke A, Möhlig M, Hoffmann K, Bergmann MM, Ristow M, Boeing H, Pfeiffer AF. Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study.. Diabetes 2003 Mar;52(3):812-7.
- Phillips CM, Perry IJ. Does inflammation determine metabolic health status in obese and nonobese adults?. J Clin Endocrinol Metab 2013 Oct;98(10):E1610-9.
- Menzies-Gow NJ, Wray H, Bailey SR, Harris PA, Elliott J. The effect of exercise on plasma concentrations of inflammatory markers in normal and previously laminitic ponies.. Equine Vet J 2014 May;46(3):317-21.
- Suagee JK, Burk AO, Quinn RW, Hartsock TG, Douglass LW. Effects of diet and weight gain on circulating tumour necrosis factor-α concentrations in Thoroughbred geldings.. J Anim Physiol Anim Nutr (Berl) 2011 Apr;95(2):161-70.
- Roach DR, Bean AG, Demangel C, France MP, Briscoe H, Britton WJ. TNF regulates chemokine induction essential for cell recruitment, granuloma formation, and clearance of mycobacterial infection.. J Immunol 2002 May 1;168(9):4620-7.
- Plomgaard P, Nielsen AR, Fischer CP, Mortensen OH, Broholm C, Penkowa M, Krogh-Madsen R, Erikstrup C, Lindegaard B, Petersen AM, Taudorf S, Pedersen BK. Associations between insulin resistance and TNF-alpha in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes.. Diabetologia 2007 Dec;50(12):2562-71.
- de Alvaro C, Teruel T, Hernandez R, Lorenzo M. Tumor necrosis factor alpha produces insulin resistance in skeletal muscle by activation of inhibitor kappaB kinase in a p38 MAPK-dependent manner.. J Biol Chem 2004 Apr 23;279(17):17070-8.
- Plomgaard P, Penkowa M, Pedersen BK. Fiber type specific expression of TNF-alpha, IL-6 and IL-18 in human skeletal muscles.. Exerc Immunol Rev 2005;11:53-63.
- Bhatt BA, Dube JJ, Dedousis N, Reider JA, O'Doherty RM. Diet-induced obesity and acute hyperlipidemia reduce IkappaBalpha levels in rat skeletal muscle in a fiber-type dependent manner.. Am J Physiol Regul Integr Comp Physiol 2006 Jan;290(1):R233-40.
- de Laat MA, McGree JM, Sillence MN. Equine hyperinsulinemia: investigation of the enteroinsular axis during insulin dysregulation.. Am J Physiol Endocrinol Metab 2016 Jan 1;310(1):E61-72.
Citations
This article has been cited 3 times.- Senderska-Płonowska M, Siwińska N, Zak-Bochenek A, Rykała M, Słowikowska M, Madej JP, Kaleta-Kuratewicz K, Niedźwiedź A. The Differences in Histoarchitecture of Hoof Lamellae between Obese and Lean Draft Horses.. Animals (Basel) 2022 Jul 11;12(14).
- Blaue D, Schedlbauer C, Starzonek J, Gittel C, Brehm W, Blüher M, Pfeffer M, Vervuert I. The influence of equine body weight gain on inflammatory cytokine expressions of adipose tissue in response to endotoxin challenge.. Acta Vet Scand 2020 Apr 22;62(1):17.
- Fitzgerald DM, Anderson ST, Sillence MN, de Laat MA. The cresty neck score is an independent predictor of insulin dysregulation in ponies.. PLoS One 2019;14(7):e0220203.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists