Glucose metabolism is essential for both neurons and muscles' normal function. However, glucose homeostasis is also tightly maintained in mammals to support all cells' function. We are interested in how glucose metabolism among different tissues affects neuromuscular function. In aging C. elegans males, we found a correlation between the decline of mating potency and the upregulation of mRNA levels of metabolic genes involved in both catabolism and anabolism of glucose, including glycolytic enzyme hexokinase (hxk-1) and cataplerotic enzyme phosphoenolpyruvate carboxykinase (pck-1 and pck-2). hxk-1 has overlapped expression with pck-1 in neurons and muscles, and overlapped expression with pck-2 in intestines and muscles. Using CRISPR-Cas9 and CRE-Lox technology, we generated homozygous and tissue specific knockouts of hxk-1. While homozygous or neuronal+muscular knockout of hxk-1 had no effect on mating potency or performance in virgin males, pharyngeal muscular+intestinal knockout significantly enhanced their mating performance in day 3 aged virgin males. These results suggest intestinal glucose catabolism might contribute to the decline of mating performance in aging C. elegans virgin males. Consistent with this, overexpression of intestinal hxk-1 can accelerate the performance decline to day 1. pck-2 knockout was previously shown to reduce glycogen and lipid content, and also can accelerate the performance decline. We found that knocking out of hxk-1 in pck-2 mutants rescues mating performance at high-, but not low-competitive setting. These results suggest that glucose homeostasis between intestine and other tissues influences mating performance. We are also interested in how the durability of the mating circuit is affected by glucose metabolism. To test this, we assayed how many females one male can impregnate in its lifetime. While hxk-1 or pck-1 single knockout showed no obvious effect on mating durability, hxk-1; pck-1 double knockout lowered the durability by 50%. This suggests the redundant function of hxk-1 and pck-1 in maintaining the durability and highlights the possible function of neuronal and muscular glucose metabolism in maintaining the durability of the mating circuit.

Affiliation:
- Biology Department, Texas A&M University, College Station, TX