High-fat diet affects autophagy and mitochondrial compartment in rat Harderian gland

The Harderian gland (HG) of Rattus norvegicus is an orbital gland secreting lipids that accumulate in excess under condition of increased lipid metabolism. To study the response elicitated by lipid overload in rat HG, we housed the animals in thermoneutral conditions (28-30 degrees C) in association to high fat diet (HFD). In HFD rats alterated blood lipid levels result in lipid accumulation in HG as demonstrated by the increased gland weight and histochemical/ultrastructural analyses. The HFD-caused oxidative stress forces the gland to trigger antioxidant defense mechanisms and autophagic process, such as lipophagy and mitophagy. Induction of mitochondrial DNA (mtDNA) damage and repair was stronger in HFD-rat HGs. An increase in marker expression levels of mitochondrial biogenesis, fission, and fusion occurred to counteract mtDNA copy number reduction and mitophagy. Therefore, the results demonstrate that rat HG activates autophagy as survival strategy under conditions of increased lipid metabolism and suggest a key role for mitophagy and membrane dynamics in the mitochondrial adaptive response to HFD.

Automated summary

This study investigates the response of the Harderian gland in rats to lipid overload caused by a high-fat diet. The researchers found that lipid accumulation in the gland leads to oxidative stress and triggers antioxidant defense mechanisms and autophagy. The damaged mitochondrial DNA in the gland is repaired through induction of mitochondrial biogenesis, fission, and fusion. The results suggest that autophagy and membrane dynamics play important roles in the gland's adaptive response to high-fat diet.