The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Relationships among inflammatory cytokines, obesity, and insulin sensitivity in the horse1,2
Abstract
Recent studies associate obesity and insulin resistance in horses with development of abnormal reproductive function and debilitating laminitis. The factors contributing to insulin resistance in obese horses are unknown. However, human studies provide evidence that elevated inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha), IL1, and IL6 play direct roles in development of obesity-associated insulin resistance. Thus, inflammation may be a key link between obesity and insulin resistance in horses. The aim of the current investigation was to examine possible relationships between obesity, inflammatory cytokines, and insulin sensitivity (IS) in the horse. Age was recorded and BCS and percent body fat (% FAT) were determined as measures of obesity in 60 mares. In addition, blood mRNA expression of IL1, IL6, and TNFalpha and circulating concentrations of TNFalpha protein (TNFp) were determined in each mare. Finally, fasted concentrations of insulin were determined, and IS was determined using the hyperinsulinemic, euglycemic clamp. Significant correlations between several variables provided evidence for the design of 4 population regression models to estimate relationships between measures of obesity, inflammatory factors, and IS in the sample population. The results of these analyses revealed that IS decreased as BCS and % FAT increased (P < 0.001) in the sample population. Additionally, increased IL1 (P < 0.05) and TNFp (P < 0.01) were associated with decreased IS. However, increased TNFalpha (P < 0.001) was associated with decreased IS only in mares 20 yr of age and older. Increased BCS and % FAT were associated with increased expression of TNFalpha (P = 0.053) and IL1 (P < 0.05), and increased TNFp (P < 0.05). Surprisingly, increased BCS and % FAT were associated with decreased IL6 expression (P = 0.05) in mares <20 yr of age. Finally, evaluation of the influence of obesity and inflammatory cytokines on IS within the same model suggested that BCS and % FAT (P < 0.001) with TNFalpha [mRNA (P = 0.07) and protein (P < 0.05)] are inversely associated with IS independently of one another. Combined, these results provide the first evidence associating obesity with increased inflammatory factors in the horse. Furthermore, the results suggest that an interrelationship exists among obesity, inflammatory cytokines, and IS in the horse and emphasize the need for further studies to elucidate the nature of these relationships.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
R: A Language and Environment for Statistical Computing
R Core Team (2025) · doi:10.32614/r.manuals · Cited by 352,181
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041
Applied Linear Statistical Models
Ziegel, E. R., Neter, J., Wasserman, W., & Kutner, M. (1992) · Technometrics · doi:10.2307/1269588 · Cited by 9,907
Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance
Hotamisligil, G. S., Shargill, N. S., & Spiegelman, B. M. (1993) · Science · doi:10.1126/science.7678183 · Cited by 7,518
Glucose clamp technique: a method for quantifying insulin secretion and resistance.
DeFronzo, R. A., Tobin, J. D., & Andres, R. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.237.3.e214 · Cited by 7,425
Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760
Applied Linear Statistical Models.
Lorenz, F., Neter, J., Wasserman, W., & Kutner, M. H. (1986) · Journal of the American Statistical Association · doi:10.2307/2289108 · Cited by 5,565
Inflamm‐aging: An Evolutionary Perspective on Immunosenescence
FRANCESCHI, C., BONAFÈ, M., VALENSIN, S., OLIVIERI, F., DE LUCA, M., OTTAVIANI, E., & DE BENEDICTIS, G. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06651.x · Cited by 5,358
Adipocytokines: mediators linking adipose tissue, inflammation and immunity
Tilg, H., & Moschen, A. R. (2006) · Nature Reviews Immunology · doi:10.1038/nri1937 · Cited by 3,188
Hotamisligil, G. S., Peraldi, P., Budavari, A., Ellis, R., White, M. F., & Spiegelman, B. M. (1996) · Science · doi:10.1126/science.271.5249.665 · Cited by 2,630
Inflammation: the link between insulin resistance, obesity and diabetes
Dandona, P. (2004) · Trends in Immunology · doi:10.1016/j.it.2003.10.013 · Cited by 2,170
Subcutaneous Adipose Tissue Releases Interleukin-6, But Not Tumor Necrosis Factor-α,in Vivo1
Mohamed-Ali, V., Goodrick, S., Rawesh, A., Katz, D. R., Miles, J. M., Yudkin, J. S., Klein, S., & Coppack, S. W. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.12.4450 · Cited by 2,012
Relationship between condition score, physical measurements and body fat percentage in mares
HENNEKE, D. R., POTTER, G. D., KREIDER, J. L., & YEATES, B. F. (1983) · Equine Veterinary Journal · doi:10.1111/j.2042-3306.1983.tb01826.x · Cited by 1,945
Kern, P. A., Saghizadeh, M., Ong, J. M., Bosch, R. J., Deem, R., & Simsolo, R. B. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117899 · Cited by 1,305
Suganami, T., Nishida, J., & Ogawa, Y. (2005) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000183883.72263.13 · Cited by 1,056 · cited 1×
“Therefore, a continuous cycle of cross talk between adipocytes and monocytes (Suganami et al., 2005) may stimulate and perpetuate the proinflammatory status associated with obesity in humans and mice.”
BackgroundInsulin Resistance and Chronic Cardiovascular Inflammatory Syndrome
Fernández-Real, J. M., & Ricart, W. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0010 · Cited by 886
Is obesity an inflammatory condition?
Das, U. N. (2001) · Nutrition · doi:10.1016/s0899-9007(01)00672-4 · Cited by 799
The role of TNFα and TNF receptors in obesity and insulin resistance
Hotamisligil, G. S. (1999) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.1999.00490.x · Cited by 780
Circulating Interleukin‐6 in Relation to Adiposity, Insulin Action, and Insulin Secretion
Vozarova, B., Weyer, C., Hanson, K., Tataranni, P. A., Bogardus, C., & Pratley, R. E. (2001) · Obesity Research · doi:10.1038/oby.2001.54 · Cited by 639
Senn, J. J., Klover, P. J., Nowak, I. A., Zimmers, T. A., Koniaris, L. G., Furlanetto, R. W., & Mooney, R. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210689200 · Cited by 620
Glucose Intolerance and Aging: Evidence for Tissue Insensitivity to Insulin
DeFronzo, R. A. (1979) · Diabetes · doi:10.2337/diab.28.12.1095 · Cited by 595
Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-α
Ruan, H., & Lodish, H. F. (2003) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(03)00052-2 · Cited by 541
Silswal, N., Singh, A. K., Aruna, B., Mukhopadhyay, S., Ghosh, S., & Ehtesham, N. Z. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.06.202 · Cited by 540
An Inflammatory Cascade Leading to Hyperresistinemia in Humans
Lehrke, M., Reilly, M. P., Millington, S. C., Iqbal, N., Rader, D. J., & Lazar, M. A. (2004) · PLoS Medicine · doi:10.1371/journal.pmed.0010045 · Cited by 518
Mechanisms of TNF-α-induced insulin resistance
Hotamisligil, G. (2009) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0029-1212086 · Cited by 418
Role of leptin as an immunomodulator of blood mononuclear cells: mechanisms of action
SÁNCHEZ-MARGALET, V, MARTÍN-ROMERO, C., SANTOS-ALVAREZ, J., GOBERNA, R., NAJIB, S., & GONZALEZ-YANES, C. (2003) · Clinical and Experimental Immunology · doi:10.1046/j.1365-2249.2003.02190.x · Cited by 357
Yang, R.-Z., Lee, M.-J., Hu, H., Pollin, T. I., Ryan, A. S., Nicklas, B. J., Snitker, S., Horenstein, R. B., Hull, K., Goldberg, N. H., et al. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030287 · Cited by 355
Obesity and diet affect glucose dynamics and insulin sensitivity in Thoroughbred geldings1
Hoffman, R. M., Boston, R. C., Stefanovski, D., Kronfeld, D. S., & Harris, P. A. (2003) · Journal of Animal Science · doi:10.2527/2003.8192333x · Cited by 320
Petrovsky, N., McNair, P., & Harrison, L. C. (1998) · Cytokine · doi:10.1006/cyto.1997.0289 · Cited by 316
Signaling Specificity of Interleukin-6 Action on Glucose and Lipid Metabolism in Skeletal Muscle
Al-Khalili, L., Bouzakri, K., Glund, S., Lönnqvist, F., Koistinen, H. A., & Krook, A. (2006) · Molecular Endocrinology · doi:10.1210/me.2005-0490 · Cited by 250
Glucose tolerance and insulin sensitivity in ponies and Standardbred horses
Jeffcott, L. B., FIELD, J. R., McLean, J. G., & O’Dea, K. (1986) · Equine Veterinary Journal · doi:10.1111/j.2042-3306.1986.tb03556.x · Cited by 243
Insulin Resistance in Type 2 Diabetes - Role of the Adipokines
Arner, P. (2005) · Current Molecular Medicine · doi:10.2174/1566524053766022 · Cited by 201 · cited 1×
“Whereas there is little information on blood mRNA expression of IL6 in relation to insulin sensitivity, several studies positively correlate serum concentrations of IL6 protein with obesity and insulin resistance in humans (Vozarova et al., 2001; Bluher et al., 2005).”
BackgroundFoals are interferon gamma-deficient at birth
Breathnach, C. C., Sturgill-Wright, T., Stiltner, J. L., Adams, A. A., Lunn, D. P., & Horohov, D. W. (2006) · Veterinary Immunology and Immunopathology · doi:10.1016/j.vetimm.2006.02.010 · Cited by 199
Self-citationBlüher, M., Fasshauer, M., Tönjes, A., Kratzsch, J., Schön, M., & Paschke, R. (2005) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2005-872851 · Cited by 193
Influence of TNF-α and IL-6 infusions on insulin sensitivity and expression of IL-18 in humans
Krogh-Madsen, R., Plomgaard, P., Møller, K., Mittendorfer, B., & Pedersen, B. K. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00471.2005 · Cited by 180
FREESTONE, J. F., WOLFSHEIMER, K. J., KAMERLING, S. G., CHURCH, G., HAMRA, J., & BAGWELL, C. (1991) · Equine Veterinary Journal · doi:10.1111/j.2042-3306.1991.tb02760.x · Cited by 167
Krogh‐Madsen, R., Plomgaard, P., Keller, P., Keller, C., & Pedersen, B. K. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00274.2003 · Cited by 155
Is obesity an inflammatory disease?
Ramos, E. J. B., Xu, Y., Romanova, I., Middleton, F. A., Chen, C., Quinn, R., Inui, A., Das, U. N., & Meguid, M. M. (2003) · Surgery · doi:10.1067/msy.2003.267 · Cited by 152
Effect of short‐term exercise training on insulin sensitivity in obese and lean mares
Powell, D. M., Reedy, S. E., Sessions, D. R., & Fitzgerald, B. P. (2002) · Equine Veterinary Journal · doi:10.1111/j.2042-3306.2002.tb05396.x · Cited by 145
Self-citationVick, M. M., Sessions, D. R., Murphy, B. A., Kennedy, E. L., Reedy, S. E., & Fitzgerald, B. P. (2006) · Reproduction Fertility and Development · doi:10.1071/rd06016 · Cited by 128
Self-citationHe, J., Usui, I., Ishizuka, K., Kanatani, Y., Hiratani, K., Iwata, M., Bukhari, A., Haruta, T., Sasaoka, T., & Kobayashi, M. (2005) · Molecular Endocrinology · doi:10.1210/me.2005-0107 · Cited by 112
Diabetes, Inflammation, and Functional Decline in Older Adults
Figaro, M. K., Kritchevsky, S. B., Resnick, H. E., Shorr, R. I., Butler, J., Shintani, A., Penninx, B. W. J. H., Simonsick, E. M., Goodpaster, B. H., Newman, A. B., et al. (2006) · Diabetes Care · doi:10.2337/dc06-0245 · Cited by 93
Insulin tolerance in laminitic ponies.
Coffman, J. R., & Colles, C. M. (1983) · PubMed · Cited by 92
Alterations in peripheral blood lymphocyte cytokine expression in obesity
O’Rourke, R. W., Kay, T., Lyle, E. A., Traxler, S., Deveney, C. W., Jobe, B. A., Roberts, C. T., Marks, D. L., & Rosenbaum, J. T. (2006) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2006.03186.x · Cited by 76
The effect of aging on T cell responses in the horse
Horohov, D. W., Kydd, J. H., & Hannant, D. (2002) · Developmental & Comparative Immunology · doi:10.1016/s0145-305x(01)00027-1 · Cited by 61
Self-citationGood, M., Newell, F., Haupt, L. M., Whitehead, J. P., Hutley, L. J., & Prins, J. B. (2006) · Diabetes and Vascular Disease Research · doi:10.3132/dvdr.2006.003 · Cited by 57
Fu, Y., Luo, L., Luo, N., & Garvey, W. T. (2006) · Nutrition & Metabolism · doi:10.1186/1743-7075-3-28 · Cited by 57
Sessions, D. R., Reedy, S. E., Vick, M. M., Murphy, B. A., & Fitzgerald, B. P. (2004) · Journal of Animal Science · doi:10.2527/2004.8282321x · Cited by 57
Self-citationEquine laminits — Another hypothesis for pathogenesis
Field, J. R., & Jeffcott, L. B. (1989) · Medical Hypotheses · doi:10.1016/0306-9877(89)90062-5 · Cited by 53
Kushibiki, S., HODATE, K., Shingu, H., Ueda, Y., SHINODA, M., Mori, Y., Itoh, T., & Yokomizo, Y. (2001) · Domestic Animal Endocrinology · doi:10.1016/s0739-7240(01)00102-3 · Cited by 49
Tumor Necrosis Factor-α Levels in Adipose Tissue of Lean and Obese Cats
Miller, C. C., Bartges, J. W., Cornelius, L. M., Norton, N. A., & Barton, M. H. (1998) · Journal of Nutrition · doi:10.1093/jn/128.12.2751s · Cited by 30
Cited by
Molecular inflammation: Underpinnings of aging and age-related diseases
Chung, H. Y., Cesari, M., Anton, S., Marzetti, E., Giovannini, S., Seo, A. Y., Carter, C., Yu, B. P., & Leeuwenburgh, C. (2009) · Ageing Research Reviews · doi:10.1016/j.arr.2008.07.002 · Cited by 1,203
Frank, N., Geor, R. J., Bailey, S. R., Durham, A. E., & Johnson, P. J. (2010) · Journal of Veterinary Internal Medicine · doi:10.1111/j.1939-1676.2010.0503.x · Cited by 421
Metadata
- Authors
- Vick, M. M., Adams, A. A., Murphy, B. A., Sessions, D. R., Horohov, D. W., Cook, R. F., Shelton, B. J., & Fitzgerald, B. P.
- Venue
- Journal of Animal Science
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-05-01
- Volume
- 85
- Issue
- 5
- Pages
- 1144-1155
- ISSN
- 0021-8812 (ISSN-L)
- 1525-3163
- OpenAlex
- W2048104199
- Cited by
- 306
- References
- 52
- FWCI
- 35.30
- Type
- journal article
- Language
- en
- Open access
- closed
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.