Investigation of the effects of FAM163A protein and mitochondrial activity in the arcuate nucleus of hypothalamus on food intake in mice

Mitochondrial function has important roles in neuronal activity and plays a role in the regulation of the activities of agouti-related peptide (AgRP) and proopiomelanocortin (POMC) neurons located in the arcuate nucleus (ARC) of the hypothalamus that regulates food intake. FAM163A is a recently discovered protein, its function and intracellular localization are not clear. The aim of our study is to examine the effect of Fam163a knockdown and mitochondrial dysfunction on AgRP neuron activity and mitochondrial activity in ARC. While Fam163a silencing increased cumulative food consumption in the short term, it did not effect on cumulative food consumption in the long term. Fam163a knockdown in ARC did not change the locomotor activity and anxiety-like behavior, while rotenone administration significantly increased the time spent in the center in the open field test (p<0.05). Fam163a silencing and rotenone administration significantly decreased AgRP activity (p<0.05). Blood glucose and serum insulin levels were not affected by rotenone administration and Fam163a silencing. Fam163a silencing dysregulated the expression of genes associated with mitophagy, mitochondrial health, and mitochondrial fusion (p<0.05). Similarly, rotenone administration significantly altered the expression of mitochondria-associated transcripts in ARC. The results of our study suggest that FAM163A has roles in hypothalamic mitochondrial activity and the regulation of mitochondria-related genes.