Lipid Metabolism in Relation to Calcium Homeostasis.

Abstract

Calcium (Ca²⁺) homeostasis is a critical regulator of insect cellular functions, influencing neurotransmission, muscle contraction, hormone signaling, and lipid metabolism. This chapter explores the intricate relationship between Ca²⁺ signaling and lipid metabolism, emphasizing key molecular components that mediate this interaction. Store-operated calcium entry (SOCE) mechanisms, involving sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA), inositol 1,4,5-trisphosphate receptor (IP₃R), ryanodine receptor (RyR), stromal interaction molecule (STIM), and Orai1, coordinate intracellular Ca²⁺ fluxes that regulate lipid storage, mobilization, and utilization. Other Ca²⁺-binding proteins, such as calmodulin (CaM), calcineurin (CaN), regucalcin (RgN), calreticulin (CrT), and calnexin (CnX), further modulate Ca²⁺ homeostasis and impact lipid metabolism by influencing lipolysis, lipogenesis, and lipid droplet dynamics. This chapter also highlights the role of hepatocyte-like oenocytes in lipid metabolism. These cells, analogous to mammalian hepatocytes, regulate lipid processing and mobilization during fasting, forming a metabolic axis with fat body adipocytes. While Ca²⁺ signaling is well characterized in adipocytes, its role in oenocyte lipid metabolism remains largely unexplored. However, Ca²⁺-dependent regulation of lipid metabolism in mammalian hepatocytes suggests a similar involvement in insect oenocytes. A central theme is the bidirectional relationship between Ca²⁺ homeostasis and lipid metabolism. While Ca²⁺ signaling regulates lipid accumulation and hydrolysis, impaired lipid metabolism can disrupt Ca²⁺ homeostasis. For instance, Drosophila melanogaster seipin mutants with defective lipid storage exhibit reduced SERCA activity, leading to lower ER and mitochondrial Ca²⁺ levels, which impair lipogenesis. Additionally, CaN promotes lipogenesis, whereas STIM and IP₃R serve as lipolytic regulators. This metabolic feedback loop is essential for maintaining energy balance. Understanding the Ca²⁺-lipid interplay in insects provides insights into metabolic regulation, with implications for pest management and metabolic disease research. Future studies should further investigate Ca²⁺-dependent mechanisms governing oenocyte function and systemic lipid homeostasis.