Fasting for long term induce digestive gland dysfunction through apoptosis despite short term salvation by autophagy using mussel model

Abstract

The stress response of fasting and extended observation of metabolic activity, antioxidant status, and transcriptomic analysis in the mussel digestive gland was reported in the present study. Our results showed that the survival rate of mussel fasting for 12 weeks was 76.15 %, and the condition factor and gonadal condition index reduced significantly after 4 weeks fasting. The ROS accumulation was significantly increased after fasting for 12 weeks, the lipid peroxidation indexes (H2O2 and MDA) were upregulated after fasting for 8 weeks, the antioxidant indexes (T-AOC, T-SOD, and CAT) were increased significantly in mussels suffering from one week fasting, then significantly decreased along with GST and GPX after long-term fasting (4, 8, 12 weeks), and the atrophy and necrosis of epithelial cells and tissue loss were observed in mussel digestive gland after long-term fasting. Changes across various metabolic regulatory pathways involved in lipid metabolism and amino acid metabolism, as well as the immunological responses were revealed by transcriptome analysis. In addition, the appearance of autophagosome and autolysosome along with the upregulation of ulk2, atg2, atg4, and Beclin1 mRNAs expression indicates autophagy was activated when fasting for one week but was relatively weakened when fasting for 8 and 12 weeks. When autophagy failed to relieve the fasting stress, apoptosis was gradually enhanced by up regulated apoptosis genes trail and bax, executing the death plan upon long-term fasting. In summary, these results indicated the transition between autophagy and apoptosis was involved in the structural and functional impairment of digestive glands in mussels caused by long-term fasting.

Keywords

• Fasting
• Mytilus coruscus
• Oxidative stress
• Autophagy
• Apoptosis