Peroxisome proliferator-activated receptor (PPAR) agonists are drugs that have been traditionally used in the treatment of metabolic syndrome, primarily for lowering triglycerides and blood sugar. PPAR agonists work by binding to cells’ peroxisome proliferator-activated receptors, biochemical sensors responsible for regulating the expression of genes. PPAR agonists have been enjoying a growing body of research in recent years pointing to their efficacy as an alcohol treatment, presenting an alternative use for the drugs.
In addition to controlling blood levels of sugar and fat, PPAR agonists were later found to act on the brain as well, possibly guarding against neurodegeneration. For example, a study published in the January 2015 issue of Alcoholism: Clinical & Experimental Research examined the effects of different classes of PPAR agonists on chronic alcohol intake in mice with a genetic predisposition for addiction, the results showed a potential use in reducing withdrawal cravings.
The University of Texas (UT) study used two different behavioral tests to measure intake of a 15 percent alcohol solution in male mice, presenting them with a 24-hour two-bottle choice and a three-hour, limited access two-bottle choice. They measured the effects of several PPAR agonists, namely pioglitazone (10 mg), fenofibrate (50 mg), GW0742 (10 mg), tesaglitazar (1.5 mg) and bezafibrate (25 mg), on alcohol intake and preference. The authors also examined genome association data for alcohol-dependent (AD) humans, looking for polymorphisms in PPAR genes linked to alcohol abuse. Using data from the Collaborative Study on the Genetics of Alcoholism (COGA), they found associations between single nucleotide polymorphisms in different PPAR genes and in those involved in alcohol dependence and withdrawal.
“[PPAR’s] job is to monitor our levels of sugars, fats, and other sources of energy and adjust our body metabolism to keep the levels of these nutrients at correct levels. However, sometimes our bodies or our diets and lifestyles cause undesirably high levels of sugar, leading to diabetes, or fats leading to hyperlipidemia, which can often be corrected by activating PPAR receptors with drugs called PPAR agonists,” said R. Adron Harris, co-author and Director of the Waggoner Center for Alcohol and Addiction Research at the University of Texas.
The researchers believe that since the brain uses many of the same signaling molecules as the immune system, they are occasionally “hijacked” by it to serve a different function, such as intercellular communication between neurons and glia. In response to excessive drinking, these neuro-immune genes become repurposed for alcohol dependency, resulting in an impairment of many of the pathways that are susceptible to regulation by PPARs. The authors suggest that this dysregulation of metabolism leads to imbalances in hormones and nutrient levels that can lead to depression and anxiety as well as impulse control issues.
A novel approach to treatment
The UT study was the first to combine human genetic studies of alcoholism with animal models of alcohol consumption in order to show a connection between PPAR receptors and alcohol abuse. Normally, finding an effective drug is followed by a lengthy FDA approval process; however, since all of the PPAR agonists used in the study were already approved, the drugs could be used “off label” for alcohol treatment.
The UT researchers plan on conducting human trials using a test group of alcoholics to see if they reduce any effects of chronic alcohol use, such as withdrawal cravings. The blood sugar/triglyceride lowering drugs have also been found to be effective in other forms of addiction as well, with several studies currently being tested on opiate addiction in humans.
Sovereign Health Group understands how alcoholism can destroy a life. They are here to help rebuild those broken lives and give back control to those who have lost so much. Sovereign utilizes a combination of therapy and medication in order to help treat those afflicted by this disease.
Chase Beckwith is a writer with Sovereign Health whose lifelong goal is to make reading about addiction and mental health palatable.