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Can diacylglycerol combat athlete hyperuricemia? Inhibiting a cardiac enzyme improves metabolism. Targeting angiopoietins to combat liver injury. Read about papers on these topics recently published in the Journal of Lipid Research.

Can diacylglycerol combat athlete hyperuricemia?

Hyperuricemia, or HUA, features high levels of uric acid, a waste product from purine breakdown and is a common issue among athletes, who are typically at lower risk of disease due to their active lifestyles. Furthermore, HUA can lead to complications like gout, kidney stones, cardiovascular disease and musculoskeletal issues. In a recent in the Journal of Lipid Research, Fangyingnan Zhang, Wei Ling Florence Lim and a team from the South China University of Technology used lipidomics and metabolomics to investigate if a diacylglycerol, or DAG, -rich diet can reduce uric acid levels in athletes with HUA.

The authors analyzed the serum lipid and metabolite levels of 33 participants with HUA, who specialized in sports such as volleyball, synchronized swimming, boxing and others. After eating a DAG-rich diet for two months, participants fell into two categories: 12 responders, whose uric acid levels normalized, and 21 nonresponders, whose levels remained high. Researchers found that responders showed significant decreases in levels of uric acid and xanthine, a precursor to uric acid that can contribute to gout.

Lipidomic studies revealed that responders showed higher plasma phosphatidylcholine, or PCO, levels and lower acylcarnitine levels. PCOs protect cells from oxidative damage; acylcarnitine promotes fatty acid transport to mitochondria, which suggests impaired lipid metabolism. These results may suggest that the DAG-rich diet increased mitochondrial fatty acid oxidation in responders, resulting in lower oxidative stress and uric acid generation. Furthermore, metabolomics revealed decreased reactive oxygen species in the responders, which likely protects plasmalogen lipids and aids in uric acid reduction.

These findings suggest that a DAG-rich diet could help treat hyperuricemia in athletes. Future research could explore DAG's mechanisms in animal models to refine factors like DAG intake levels and associated exercise intensity.

Inhibitiing a cardiac enzyme improves metabolism

Lipid metabolism is essential for cardiac function as fatty acids, or FAs, are cardiomyocytes' main energy source. The enzyme stearoyl-CoA desaturase, or SCD, converts saturated fatty acids, like stearate and palmitate, into monounsaturated fatty acids, like oleate and palmitoleate. SCD4 is a heart-specific enzyme essential for maintaining cardiac lipid metabolism.

In a recent published in the Journal of Lipid Research, Marcin Wolosiewicz and a team from the Nencki Institute of the Polish Academy of Sciences investigated the role of SCD4 in cardiac and systemic metabolism in mice that lack SCD4 fed a high-fat diet. They showed that SCD4 deficiency lowered cardiac triglyceride accumulation by increasing lipolysis and adipose triglyceride lipase activity in animals fed a high-fat diet. Mice lacking SCD4 were protected from high-fat diet–induced cardiac remodeling, which preserved their heart structure and prevented ventricular hypertrophy. In addition, SCD4-deficient mice showed improved systemic metabolic health, including reduced body weight, visceral fat loss and lower glucose and cholesterol levels. In addition, the authors showed that SCD4 deficiency inhibited mitochondrial enlargement and dampened activity of the nicotinamide adenine dinucleotide dehydrogenase, the first complex of the electron transport chain, further protecting the mice from oxidative stress.

These results suggest that targeting SCD4 could serve as a potential therapy for preventing diet-induced cardiac and metabolic diseases. Future research will focus on exploring the therapeutic potential of targeting SCD4 to prevent or treat diet-induced cardiac and metabolic diseases in clinical settings.

Targeting angiopoietins to combat liver injury

Sepsis is a life-threatening illness that causes widespread organ failure due to an overactive immune response to infection. While sepsis affects multiple organs, liver damage is a particularly serious consequence that increases the risk of organ failure. During sepsis, the liver, which is essential for metabolic and immunological homeostasis, gets damaged by inflammatory reactions and altered lipid metabolism. Angiopoietin-like protein 8, or ANGPTL8, regulates glucose and lipid metabolism and has been associated with inflammation and liver damage.

In a recent published in the Journal of Lipid Research, Ying Feng, Shan Luo, Chen Fang and a team from Hubei University of Medicine explored the effects of ANGPTL8 deficiency on liver injury during sepsis. The authors used lipopolysaccharide, or LPS, a bacterial toxin, to induce sepsis in mice. They first showed that LPS treatment elevated liver ANGPTL8 and causes lipid accumulation in normal mice. Furthermore, the authors showed that mice lacking ANGPTL8 showed decreased lipid accumulation, increased fatty acid oxidation and improved liver function, which led to higher sepsis survival rates.

The researchers also showed that LPS-induced ANGPTL8 expression depends on TNFα, an inflammatory cytokine. Targeting ANGPTL8 could be a promising therapeutic method for treating sepsis-related liver dysfunction by lowering inflammation and improving metabolic balance. Given that sepsis is characterized by multiple organ dysfunction, investigating the role of ANGPTL8 in lung injury, kidney injury and other organ damage is crucial for guiding the development of ANGPTL8-targeted therapies.