Novel Function of Insulin‐Like Peptides: Signaling in Sickness‐Induced Anorexia (SIA)

Often, when an organism becomes ill, it stops feeding. Yet, somehow most animals are able to regain their health and overcome the illness. This phenomenon is called sickness‐induced anorexia (SIA). SIA is hypothesized to be an adaptive function that reallocates energy toward immune function. Most animals exhibit SIA, yet what triggers it and the mechanisms tying it to immunity remain unknown. One potential mediator of SIA is insulin signaling. Both vertebrates and invertebrates share a conserved insulin‐signaling pathway, but how this pathway regulates feeding behavior and dietary intake is not yet well understood. In insects, the storage tissue known as the fat body plays a key role in assessing nutritional status, such as amino acid content, to secrete insulin‐like peptides (ILP). Although various ILP have been found in insects, their physiological functions are largely unknown. Much like insulin in vertebrates, ILP have been shown to block synthesis of blood sugar (trehalose) from dietary sugars and amino acids and promote the consumption of glycogen reserves. When carbohydrate levels are high, fat body cells signal to ILP‐producing cells via the target of rapamycin (TOR) pathway to secrete ILP. This study aims to elucidate a mechanism between ILP secretion and SIA and to discover novel functions of ILP using the tobacco hornworm caterpillar, Manduca sexta , an insect that has been shown to exhibit SIA. To determine if ILP secretion is required for SIA, ILP will be manipulated in both the presence and absence of an immune challenge. ILP levels will be manipulated by either blocking with wortmannin, a downstream inhibitor of insulin‐signaling, or increasing with bovine insulin, which has been shown to have similar effects as ILP in insects. During SIA from a bacterial infection, blocking or increasing ILP are expected to result respectively in no glycogen consumption and glycogen exhaustion. With the lack of nutrient availability from either feeding or glycogen storage, we expect survival of a bacterial infection to decrease. However, if ILP secretion is blocked then recovered by bovine insulin injection, we would expect survival to increase. As a result of these changes, fat body content and trehalose concentrations are expected to change. Clarifying what mediates SIA would have a broad impact on nutritional, immunological, and developmental studies in all types of organisms.