Roles of Insect Oenocytes in Physiology and Their Relevance to Human Metabolic Diseases


Oenocytes are large secretory cells present in the abdomen of insects known to synthesize very-long-chain fatty acids to produce hydrocarbons and pheromones that mediate courtship behavior in adult flies. In recent years, oenocytes have been implicated in the regulation of energy metabolism. These hepatocyte-like cells accumulate lipid droplets under starvation and can non-autonomously regulate tracheal waterproofing and adipocyte lipid composition. Here, we summarize evidence, mostly from Drosophila, establishing that oenocytes perform liver-like functions. We also compare the functional differences in oenocytes and the fat body, another lipid storage tissue which also performs liver-like functions. Lastly, we examine signaling pathways that regulate oenocyte metabolism derived from other metabolic tissues, as well as oenocyte-derived signals that regulate energy homeostasis.


Regulating energy utilization and storage is central to animal physiology and adaptation to environmental challenges. Under conditions of nutrition surplus, glucose is converted to fatty acids, which are then synthesized into triglycerides (TGs) and stored as lipid droplets. Excessive lipid stores can be detrimental and have been associated with various metabolic diseases, such as cardiovascular diseases (CVDs), non-alcoholic fatty liver disease (NAFLD), obesity and insulin resistance, making understanding lipid metabolism of great importance to human health.

The liver is the major detoxifying organ of the body and plays a central role in regulating the metabolism of carbohydrates, proteins and lipids. Moreover, the liver is the major site for glycogen storage and very low-density lipoprotein (VLDL) secretion (12). During starvation, adipocytes undergo lipolysis to produce free fatty acids (FFAs). FFAs are processed by hepatic oxidation to generate ketone bodies in the liver which are then used as fuels for other tissues. If mobilization of FFAs exceeds the rate of lipid oxidation, re-esterification of surplus FFAs to TGs occurs in the liver, leading to an increase in intrahepatic TG content, i.e., steatosis. NAFLD, a common manifestation of the metabolic syndrome, is characterized by steatosis in the absence of starvation. Nonalcoholic hepatic steatosis is present in approximately 25% of the adult population worldwide, and NAFLD is the most common liver disease in Western societies. Thus, understanding how hepatic diseases regulate cellular processes in peripheral organs and how other organs contribute to steatosis is of interest to human metabolic diseases.

Major metabolic and endocrine pathways are conserved in Drosophila, making this model organism well suited to dissect the cellular and molecular mechanisms underlying physiology (35). The fly fat body is equivalent to the vertebrate white adipose tissue (WAT), which stores excess fat as TGs. In addition, fly oenocytes, which are similar to hepatocyte cells, are important for mobilizing stored lipids from the fly fat body (6). Like mammals, flies convert excess carbohydrates into TGs through de novo lipogenesis (78). In addition, excess carbohydrates and amino acids can also be processed into UDP-glucose, which fuels glycogen synthesis (9). Regulation of energy storage in flies involves several signaling pathways, including insulin/insulin-like growth factor (IGF) signaling, which is similar to the insulin signaling in mammals (10). However, unlike mammals, there are eight different Drosophila insulin-like peptides (dILPs). Most of these modulate the IGF pathway through a single insulin receptor, InR (1011). Under nutrient-deprivation or energy demanding conditions, lipids are released from the fat body through increased lipolysis (12), and are further processed in oenocytes (613). Signaling that regulates catabolism of lipids and carbohydrates include adipokinetic hormone (Akh), which is similar to glucagon in mammals and ecdysone, which antagonizes insulin signaling (1415).

In this review, we explore the potential of Drosophila oenocytes as a model for hepatic diseases. We summarize the different roles of oenocytes and the fat body in regulating carbohydrate and lipid metabolism under normal or starved conditions. We also discuss the intricate interplay of oenocytes with other tissues, including the fat body and muscles, in shaping organismal lipid storage.

Publisher's Version

See also: Review Article