Quality of fat input determines kidney and cardiac health and repair

April 18, 2022

New research by a University of South Florida lab team describing how certain fats can harm or repair the heart after injury has been accepted by a journal of the American Physiological Society, according to a news release.

A manuscript by Ganesh Halade, PhD, an Associate Professor of Cardiovascular Sciences at the USF Health Morsani College of Medicine and a researcher in the USF Health Heart Institute, appears in the American Journal of Physiology-Heart and Circulatory Physiology.

A key message of the manuscript is how a certain type of healthy fat known as docosahexaenoic acid (DHA) – which is present in Omega-3 fish oil, as found in salmon and tuna – works in tandem with enzymes from the spleen to clear the inflammation in a damaged heart. The spleen plays an important role because it sends immune cells with bags of healthy fat that operates cardiac repair after major injury such as a heart attack.

“So, the fat intake needs to be of optimal quality and used by the right enzyme of immune cells,’’ Halade said. “This is all about cardiac repair and the inflammation clearing molecules (resolution mediators) involved in that repair. It’s essential to the resolution process.’’

Another key message is more about prevention and the genesis of cardiovascular disease: How a chronic and surplus dietary intake of safflower oil (SO, omega-6) can lead to residual inflammation of spleen, kidney, heart, and biosynthesis of pro-inflammatory mediators after an ischemic event. SO is a type of fat commonly used in processed and fast foods that drives chronic inflammation.

“The big question for most people is whether a fat is good or bad, or is omega-3 helpful for heart health?’’ Halade said. “Everyone is dealing with this question. We’re thinking beyond that by looking at how fat is used in the body after a heart attack and in what forms.’’

“All fats are not created equal,’’ he added, “and despite the extensive literature, the effect of fat intake is the most debated question in obesity, cardiovascular, and cardiorenal research.’’

In his research, Dr. Halade and his team put 100 mice on a 12-week diet of processed (SO) foods to develop residual inflammation and then 50 mice randomized on a primarily DHA-enriched diet for next eight weeks before subjecting to ischemic surgery in mice.

The team made sure both diets had same quantity of calorie per gram of diet. The surplus and chronic intake of SO increased inflammation along with a dysfunctional cardiorenal network. In contrast, DHA increased survival following such heart damage (heart attack).

A result of the study was that the alignment of immune cell enzymes from the spleen and DHA fats are essential to cardiac repair. These so-called “resolution mediators (a family of specialized pro-resolving mediators) is the body’s natural defense process without a negative impact on the body’s physiological response,’’ Halade said.

Among the key findings in the study:

  • DHA supplement improved survival after experimental heart attack to mice
  • DHA boost safe clearance of inflammation (resolution) from an injured heart without change in the acute phase of the inflammatory response (day 1), with increased expression of Arg-1, MRC-1, and YM-1 in spleen and infarcted area. These agents are resolution and reparative markers of immune response.
  • DHA, along with the body’s natural enzymes, enhanced the ability for the spleen and heart to work together in repairing damage.
  • SO primed the spleen and kidney to induce pro-inflammatory pathways and renal inflammation.

“Our next step is to determine the enzymatic machinery or immune responsive enzymes that biosynthesize resolution mediators after ischemic (decreased blood flow commonly called a heart attack) event,’’ Halade said.

Part of Halade’s research focuses on how unresolved chronic inflammation and immune responsive metabolic dysregulation contributes to ischemic and non-ischemic heart failure. He is involved in studies of heart failure etiology with an integrative approach focusing on splenic leukocytes and heart, as well as the measurement of inflammatory mediators that impair cardiac repair and resolving lipid mediators that facilitate cardiac repair after a heart attack.

Halade hopes his latest work can shed new light on controlling chronic inflammation and treating heart failure — a progressively debilitating condition in which weakened or stiff heart muscle cannot pump enough blood to meet the body’s demand for nutrients and oxygen.

It has become a growing public health problem, fueled in part by an aging population, poor diet, and obesity epidemic. About 6.2 million adults in the U.S. suffer heart failure, according to the Federal Centers for Disease Control and Prevention.

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