Resistin levels in horses linked to inflammation, not insulin problems

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Resistin is an adipokine - one of a range of cell-signalling molecules related to adipose tissue (body fat).
Resistin is an adipokine – one of a range of cell-signalling molecules related to adipose tissue (body fat). File image. Photo by Navid Bazari

Serum levels of resistin in horses appear to be a reliable measure of inflammation but not insulin problems, researchers report.

Resistin is an adipokine, one of a range of cell-signaling molecules related to adipose tissue (fat). Researchers, writing in the journal Animals, described fat tissue as a key endocrine organ that communicates with other organs by multiple endocrine substances – adipokines.

There is evidence that adipokines may contribute to the regulation of biological processes, such as metabolism, immunity, and inflammation.

Beatriz Fuentes-Romero and her fellow researchers in Spain set out to investigate the diagnostic usefulness of resistin, and its relationship with insulin dysregulation and inflammation in horses.

Their study involved 72 horses, divided into four groups. There were 14 healthy controls, 21 horses with inflammatory conditions, 18 with mild insulin dysregulation, and 19 with severe insulin dysregulation.

The study team found that plasma resistin concentrations were significantly different between the groups, with the highest values recorded in the inflammatory and severe insulin dysregulation groups.

They found no correlation between plasma resistin and basal insulin concentrations, but there was a significant correlation between resistin levels and the acute phase protein serum amyloid A.

These two findings suggest that, as is the case in humans, plasma resistin concentrations in horses are mostly related to inflammatory conditions and not to insulin dysregulation, they said.

“Horses with severe insulin dysregulation showed an elevation in resistin that may be secondary to the inflammatory status associated with metabolic syndrome.”

Discussing their findings, the authors said the results show that resistin can be reliably measured in equine plasma and that plasma resistin concentrations increase preferentially in horses with inflammatory conditions as opposed to horses with insulin dysregulation.

The diagnostic value of resistin has been reported to differ between species, they noted. While in some species, such as rodents, plasma resistin concentrations increase with obesity and metabolic syndrome, in other species, like humans, plasma resistin concentrations increase with inflammatory problems.

These differences are probably related to the cellular origin of resistin, they said. In mice, resistin is produced mainly by adipocytes, whereas in humans, it is generated mostly in peripheral blood mononuclear cells, macrophages, and bone marrow cells.

“As far as we know, there is still no report on the origin of resistin in horses,” they said.

The authors said plasma resistin concentrations were consistently elevated in horses with inflammatory problems, with results similar to those described in humans.

The mechanisms that influence the elevation of resistin associated with inflammation are not well known, they noted.

Resistin has been shown to be involved in the control of blood glucose, lipid metabolism, regulation of pituitary somatotropin cells, and the hypothalamic center of satiety.

However, the role of resistin in obesity and insulin dysregulation is highly controversial, they said.

“It has been proposed that adipokines may contribute to insulin dysregulation in mice, but other studies have argued that the insulin dysregulation mediated by resistin is not reproducible in humans.

“Human studies have shown that individuals with severe insulin resistance have higher resistin levels than healthy individuals. However, so far, the mechanisms by which insulin resistance may modulate resistin in humans are not clear.”

Findings to date suggest that, in horses, the relationship between resistin and insulin may be similar to that in humans.

“The increase in resistin in horses with severe insulin dysregulation may be related to the inflammatory changes associated with metabolic syndrome.

“Chronic inflammation is a major and well-known cause of obesity-induced insulin resistance, and several pro-inflammatory cytokines play an important role in its pathophysiology.

“Low-grade chronic inflammation associated with excessive accumulation of adipose tissue and hyperinsulinemia were reported in both humans and horses.”

The main characteristics of equine metabolic syndrome include obesity, insulin resistance, and laminitis, as well as lipid irregularities, high blood pressure, reproductive issues in mares, and an increase in inflammatory markers.

Resistin, they said, may be helpful in further exploring the connection between vascular disorders in the context of laminitis related to equine metabolic syndrome, systemic inflammatory response syndrome, and endotoxemia.

“In this sense, it would be particularly useful to determine if increased resistin values in a horse with metabolic syndrome may have any predictive value for detecting the risk of laminitis.”

The authors said future studies will be needed to better understand the diagnostic value of resistin in a spectrum of inflammatory conditions and to determine if levels may have diagnostic value to evaluate the inflammatory status in horses with insulin dysregulation.

The study team comprised Fuentes-Romero, María Martín-Cuervo and Manuel Iglesias-García, with the University of Extremadura; Alberto Muñoz-Prieto and José Cerón, with the University of Murcia; and Escolástico Aguilera-Tejero and Elisa Díez-Castro, with the University of Córdoba.

Fuentes-Romero, B.; Muñoz-Prieto, A.; Cerón, J.J.; Martín-Cuervo, M.; Iglesias-García, M.; Aguilera-Tejero, E.; Díez-Castro, E. Measurement of Plasma Resistin Concentrations in Horses with Metabolic and Inflammatory Disorders. Animals 2022, 12, 77. https://doi.org/10.3390/ani12010077

The study, published under a Creative Commons License, can be read here.

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