The Horse

OCT 2018

The Horse:Your Guide To Equine Health Care provides monthly equine health care information to horse owners, breeders, veterinarians, barn/farm managers, trainer/riding instructors, and others involved in the hands-on care of the horse.

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Page 33 of 51

34 October 2018 The Horse | IT'S ALL CONNECTED but function to regulate metabolism. Fat cells enlarging with obesity synthesize greater amounts of cytokines to disrupt metabolism in adipose tissue (another key energy reserve) and skeletal muscle. This leads to development of insulin resis- tance. In response, the pancreas secretes more insulin to signal muscle cells to take up glucose for the critical task of prevent- ing hyperglycemia. Additionally, adipose tissue harbors macrophage white blood cells, which as part of the immune system produce and secrete cytokines." There is a great deal of "cross-talk" between macrophages and adipocytes, she adds. Originally, Suagee-Bedore thought glucose or insulin in the bloodstream signaled cells to synthesize inflammatory mediators. "During glucose and insulin intravenous infusion studies, we see some increase in circulating and tissue level inflammation," she says. While this might be part of the prob- lem, she offers an additional theory: "There may be another mechanism related to intestinal changes during feed consumption, such as fermentation of glucose to lactic acid that kills off gut bacteria. Release of lipopolysaccharide (LPS, also called endotoxin, which is a component of Gram-negative bacteria cell walls) from dying bacteria interacts with the immune system—either in the gut or systemically—to result in inflam- mation. Glucose and plasma LPS peak around two hours (after feeding), yet the IL-1β increase comes more quickly at one hour post-feeding, possibly from gut macrophages." If LPS and other substances can pass out of the intestinal tract into the systemic circulation—known as leaky gut syndrome—a cascade of inflammatory events occurs bodywide. Leaky Gut Syndrome The intestinal tract is a huge contributor—as much as 70%—to the body's immune system and tends to be the cause of many problems. "The equine intestinal tract is lined by a single layer of barrier cells (called en- terocytes) to prevent toxins and bacteria from accessing the bloodstream," says Li- ara Gonzalez, DVM, PhD, Dipl. ACVS, as- sistant professor of gastroenterology and equine surgery at North Carolina State University, in Raleigh, who studies topics related to intestinal cell integrity and stem cell rejuvenation of the intestinal lining (the epithelium). "This protective barrier is very sensitive to small changes from stress, colic, or disease. The single layer of cells is created from intestinal stem cells (that reside within the horse). Incredibly, in a healthy horse, those cells proliferate and renew to create a new intestinal lining within a few days to a week's time." Intestinal epithelial cells are connected via tight junctions—protein complexes that form selective permeable seals that regulate what can and cannot pass into the bloodstream. Disruption of those junctions leads to leaky gut syndrome. "Even an intense exercise event can result in some leakiness in the GI tract," says Gonzalez. "Any stress—rigorous exercise, heat stress—that shunts blood to privileged organs (e.g., brain, kidneys) and not to the gut decreases intestinal blood flow and oxygen to the intestinal lining. Epithelial cells are very sensitive to oxygen deficits, with the resulting cell injury and loss of tight junctions causing leaky gut. "When bacteria or inflammatory me- diators cross into the bloodstream, there can be systemic signs of inflammation," she adds. "Some degree of inflamma- tion is necessary and appropriate for the healing process. However, if a horse is un- able to compensate in the face of excess inflammation, then inflammatory media- tors create a vicious cycle of unchecked whole-body inflammation." Researchers have found that leaky gut can lead to other types of systemic in- flammation, such as skin allergies (hives, itching) or laminitis (inflammation of the laminae, which connect the hoof wall to the coffin bone within). Fortunately, "the intestinal tract has an amazing capacity to repair its epithelial barrier, referred to as restitution," Gonza- lez says. If a horse in unable to compensate in the face of excess inflam- mation, then inflamma- tory mediators create a vicious cycle of unchecked whole-body inflammation." DR. LIARA GONZALEZ Stresses such as intense exercise can cause inammatory mediators to leak out of the gastrointesti- nal tract and into the bloodstream. ISTOCK.COM

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