Dietary fatty acid breakthrough: Linoleic acid emerges as rosacea therapy via restoring mitochondrial rebellion

A groundbreaking study led by researchers at Central South University demonstrated that linoleic acid (LNA), a dietary fatty acid, significantly mitigates rosacea symptoms by repairing mitochondrial damage in keratinocytes and reduces the risk of rosacea in general population, using human clinical data, animal models, cell models and UK Biobank data.

Rosacea, as a chronic, progressive inflammatory skin disorder, is featured by flushing, erythema, telangiectasia, papules/pustules and hyperplasia on the central face. Approximately 5.46% of people worldwide suffer from this disease, imposing a significant psychological burden. However, the therapeutic effect of most interventions is not satisfactory.

Prof. Zhili Deng, from Department of Dermatology, Xiangya Hospital, Central South University, China, says, "The previous research of our team has confirmed that in addition to genetic predisposition and dysfunctions in vascular, neural, and immune systems, metabolic dysregulation also contributes to rosacea progression. But here's the hitch: we still don't get HOW wonky lipid metabolism—especially fatty acids—regulates rosacea. Figuring this out could crack open better treatments."

Building on serum metabolites analysis in rosacea, researchers have identified linoleic acid (LNA) as a key therapeutic candidate, and further demonstrated that LNA prevents rosacea-like dermatitis in LL37-induced rosacea-like mouse model. Evidence showed that PPARγ signaling is hyperactivated via LNA in the epidermis of both rosacea patients and rosacea-like mouse model. Inhibiting PPARγ rescued the effect of LNA in LL37-induced mice.

Additionally, both in vivo and in vitro studies strongly supported the presence of mitochondrial damage in the keratinocytes of rosacea. LNA stimulated PPARγ to reduce the production of ROS, increase the generation of ATP and recover mitochondrial membrane potential, which eventually treat rosacea by promoting mitochondrial function.

Finally, through prospective cohort study from UK Biobank and LDSC regression analysis, researchers further confirmed a negative correlation between LNA levels and the risk of rosacea, highlighting LNA as a promising therapeutic strategy for rosacea.

Prof. Ji Li, from Xiangya Hospital, Central South University, China, concluded, " Our research discovered disrupted linoleic acid metabolism in rosacea patients, revealing its crucial role in repairing epidermal mitochondrial dysfunction. This breakthrough not only illuminates the interplay between fatty acid metabolism and oxidative stress in keratinocytes of rosacea, but also unlocks promising therapeutic strategies for rosacea and other inflammatory skin disorders.