New Fat Source Shows Promise in Fighting Obesity

A recent study led by Eric S. Goetzman, PhD, professor of Pediatrics in the Division of Genetic and Genomic Medicine at UPMC Children’s Hospital of Pittsburgh has revealed new insights about the use of dietary dicarboxylic acids in relation to metabolic disorders like obesity.

Dr. Goetzman is principal investor of the Goetzman Laboratory which has a focus on the regulation of fatty acid oxidation and its implications for diseases such as diabetes, obesity, and cancer.

The study, “Dietary dicarboxylic acids provide a non-storable alternative fat source that protects mice against obesity” was recently published in the Journal of Clinical Investigation and focuses on dodecanedioic acid (DC12), a 12-carbon dicarboxylic acid, as a unique fat source that could help prevent obesity.

Accompanying the study is a commentary on its findings and potential clinical implications.

Collaborating on the study with Dr. Goetzman was the Sims-Lucas Laboratory in the Division of Pediatric Nephrology at UPMC Children’s, led by Sunder Sims-Lucas, PhD. Also contributing to the investigation from the University of Pittsburgh were faculty from the Department of Pharmacology and Chemical Biology, Department of Pathology, the Vascular Medicine Institute, and the Health Sciences Mass Spectrometry Core. Also collaborating on the study were researchers from The Buck Institute for Research on Aging.

What is Dodecanedioic Acid (DC12)?

Dodecanedioic acid (DC12) is a 12-carbon dicarboxylic acid that can serve as an alternative dietary fat source. The molecular structure of DC12 allows it to be metabolized in the body in a different way comparted to other lipids like triglycerides. DC12 increases metabolic rate, reduces body and liver fat, and improves glucose tolerance without being stored in the body, making it a potential therapeutic option for combating obesity or other metabolic disorders.

About the Study: Overview and Summary of Findings

In their experiments, Dr. Goetzman’s team fed a small animal model either a high-fat diet (HFD) or an isocaloric diet containing DC12 for nine weeks. The objective was to understand how DC12 affects metabolic rate, body fat, liver fat, and glucose tolerance. The study also probed how DC12 may be metabolized in different tissues.

“Normally, when we consume fatty acids, our bodies prefer to store them in the liver and adipose tissue for a rainy day,” says Dr. Goetzman. “In our study, when mice were maintained on DC12 as an alternative fat source, it was immediately burned upon consumption, even within the adipose tissues. The resulting increase in energy expenditure was associated with overall improved metabolic health.”

Among the findings from the study, Dr. Goetzman and colleagues found that the animal models that consumed DC12 showed a higher metabolic rate and significantly less body and liver fat accumulation compared to those on the high-fat diet. The models also had better glucose tolerance and did not develop the insulin resistance commonly associated with high-fat diets. Breakdown products of DC12 were detected in various tissues, including the liver, kidney, muscle, heart, and brain, indicating its widespread use in the body in cellular metabolic processes.

In tissues with high levels of the enzyme acyl-CoA oxidase-1 (ACOX1), which is essential for fatty acid oxidation, DC12 was broken down to succinyl-CoA, an intermediate step required in the TCA cycle (the TCA cycle is synonymous with the Krebs cycle for energy production by the mitochondria within cells). In tissues with lower fatty acid oxidation capacity, DC12 was metabolized by mitochondria. Importantly, DC12 was not stored in the cells, supporting its role as a non-storable fat source.

Potential Implications or Translation for Clinical Practice

The outcomes of Dr. Goetzman and colleagues’ research suggest that dietary dicarboxylic acids like DC12 could be a valuable tool in managing obesity and other metabolic disorders. By increasing energy expenditure and preventing fat accumulation, DC12 offers a novel way to address obesity, especially for individuals with metabolic challenges.

“While there is much more research to be done, we envision that DC12 and other dicarboxylic acids may become a fourth class of macronutrient, accompanying carbohydrate, protein, and traditional fats in our diet,” says Dr. Goetzman.  “Clinically, they may be especially useful for treating genetic disorders of metabolism, in which inherited enzyme deficiencies prevent patients from using one or more of the three traditional macronutrients.”

Reference

Goetzman ES, Zhang BB, Zhang Y, et al. Dietary dicarboxylic acids provide a non-storable alternative fat source that protects mice against obesity. J Clin Invest. 2024.134(12): e174186.

Additional Reading

Learn more about the Goetzman Lab. and its research on fatty acid oxidation and its role in multiple disease processes, including AKI.

Learn more about the Sims-Lucas Lab and its research on the cellular mechanisms of AKI.