Fat Body

The fat body is the central metabolic, nutrient-sensing, endocrine, and systemic innate immune organ of insects, combining within a single distributed tissue the physiological functions performed separately in vertebrates by the liver and adipose tissue (Arrese & Soulages, 2010; Li et al., 2019). Derived from the embryonic mesoderm and suspended inside the open circulatory cavity (hemocoel) as thin, fenestrated sheets, ribbons, or lobes wrapped around the alimentary canal (perivisceral fat body) and beneath the body-wall epidermis (parietal / subcuticular fat body), this architecture maximizes surface-area contact with the circulating hemolymph. Across holometabolous and hemimetabolous insects—including mosquito disease vectors, agricultural pests, and pollinators—the fat body coordinates larval growth, metamorphic remodeling, diapause energy provisioning, anautogenous egg yolk synthesis (vitellogenesis), and the rapid systemic secretion of antimicrobial peptides (AMPs) upon microbial invasion.

Although visually homogeneous under low-power microscopy, the insect fat body is organized into five functionally specialized cell types whose proportions vary across orders and developmental stages (Haunerland & Shirk, 1995; Roma et al., 2010):

1. Carbohydrate Metabolism and Trehalose Homeostasis

Whereas vertebrates maintain blood glucose at ~4–6 mM, the primary circulating sugar in insect hemolymph is trehalose (α-D-glucopyranosyl-(1→1)-α-D-glucopyranoside), a non-reducing disaccharide formed by two glucose units linked at their anomeric carbons (C1–C1):

• Because trehalose lacks a free aldehyde or ketone group, it does not undergo non-enzymatic Maillard glycation of hemolymph proteins even at concentrations of 20 to 150 mM (10- to 30-fold higher than mammalian blood glucose), and acts as a bioprotective vitrifying cryoprotectant and anhidrobiotic stabilizer during winter diapause and drought.
• Trophocytes take up dietary glucose from the midgut, store it as glycogen, and synthesize trehalose via the coupled enzymes trehalose-6-phosphate synthase (TPS) and trehalose-6-phosphate phosphatase (TPP). During flight or starvation, neuropeptide Adipokinetic Hormone (AKH)—the insect functional analogue of mammalian glucagon, secreted by the corpora cardiaca—binds its G-protein-coupled receptor (AKHR) on trophocytes, activating glycogen phosphorylase via cAMP and Ca²⁺ to flood the hemolymph with trehalose.

2. Lipid Storage, Brummer Lipase, and the Reusable Lipophorin Shuttle

Over 90% of fat-body lipid is stored in cytosolic lipid droplets as anhydrous triacylglycerol (TAG), which yields six times more metabolic energy per gram of hydrated tissue than glycogen—essential for long-distance migratory insects (such as monarch butterflies Danaus plexippus and desert locusts Schistocerca gregaria) and blood-feeding vectors between gonotrophic cycles:

• Lipolysis is controlled by two Evolutionarily conserved pathways acting in parallel: (1) AKH → AKHR → cAMP → Protein Kinase A (PKA), which phosphorylates Perilipin 1 (Lsd-1) to open access to the lipid droplet surface; and (2) Brummer lipase (Bmm), the insect orthologue of mammalian adipose triglyceride lipase (ATGL), whose transcription is repressed by insulin/TOR signaling during feeding and induced by FOXO during starvation (Grönke et al., 2005).
• The Reusable Lipophorin Shuttle: Unlike vertebrate VLDL and LDL lipoproteins—which are endocytosed and degraded inside target cells after delivering their lipid cargo—insect fat-body trophocytes secrete High-Density Lipophorin (HDLp), which operates as a reusable molecular shuttle (Canavoso et al., 2001). HDLp loads diacylglycerol (DAG) from the midgut or fat body (converting into Buoyant Low-Density Lipophorin, LDLp, stabilized by apolipophorin-III), unloads DAG at the flight muscles or developing ovaries via membrane-bound lipoprotein lipase without being internalized, and returns to the fat body as HDLp to pick up another load.

3. Hexamerins (Arylphorins and Methionine-Rich Storage Proteins)

During the final larval instar of holometabolous insects, fat-body trophocytes synthesize massive quantities of hexamerins (~500 kDa homohexameric or heterohexameric proteins, evolutionarily derived from arthropod hemocyanins that lost their copper-binding oxygen-transport sites), which reach 60% to 80% of total hemolymph protein. Just before pupation, a pulse of 20-hydroxyecdysone (20E) triggers the fat body to re-internalize circulating hexamerins via receptor-mediated endocytosis into crystalline protein storage granules, providing the amino-acid and aromatic-ring (tyrosine/phenylalanine) pool needed to build adult flight muscles and sclerotize the adult cuticle during the non-feeding pupal stage (Burmester, 1999).

In anautogenous disease vectors such as Aedes aegypti and Anopheles gambiae, the fat body serves as the central metabolic sensor that couples vertebrate blood feeding to egg production (Roy et al., 2016):

• After a blood meal, free branched-chain amino acids (L-leucine) absorbed from the midgut enter fat-body trophocytes via the cationic amino acid transporter Slimfast and activate the Target of Rapamycin Complex 1 (TORC1), while brain-secreted Insulin-Like Peptides (ILPs) activate the InR–PI3K–Akt cascade and ovarian 20-hydroxyecdysone (20E) binds the nuclear Ecdysone Receptor / Ultraspiracle (EcR/USP) heterodimer.
• Acting synergistically on the promoters of yolk protein genes, TORC1 (via S6K) and EcR/USP induce a 1,000- to 10,000-fold transcriptional burst of Vitellogenin (Vg), lipophorin, and vitellogenic carboxypeptidase. Trophocytes secrete hundreds of micrograms of vitellogenin into the hemolymph over 24–36 hours, after which the fat body undergoes programmed autophagic remodeling to reset for the next gonotrophic cycle (Bryant & Raikhel, 2011).

Discovered in Drosophila by Bruno Lemaitre and Jules A. Hoffmann (1996, Nobel Prize in Physiology or Medicine 2011), the fat body is the primary effector organ of the insect humoral innate immune system (Lemaitre & Hoffmann, 2007):

1. The Toll Pathway (Fungi and Gram-Positive Lys-Type Peptidoglycan): Circulating pattern-recognition receptors (PGRP-SA, GNBP1, GNBP3) detect fungal β-1,3-glucans or Gram-positive bacterial peptidoglycan and activate a hemolymph serine-protease cascade (Persephone / Spätzle-Processing Enzyme) that cleaves pro-Spätzle into active Spätzle cytokine. Spätzle binds the transmembrane Toll receptor on fat-body trophocytes, signaling through MyD88–Tube–Pelle to phosphorylate and degrade the inhibitor Cactus (IκB), releasing the NF-κB transcription factors Dif and Dorsal (or REL1 in mosquitoes) into the nucleus to transcribe antifungal and antibacterial peptides (Drosomycin, Metchnikowin, Defensin, Cecropin).
2. The IMD (Immune Deficiency) Pathway (Gram-Negative DAP-Type Peptidoglycan): Transmembrane receptor PGRP-LC on fat-body cells directly binds meso-diaminopimelic acid (DAP)-type peptidoglycan of Gram-negative bacteria (and regulates Plasmodium falciparum resistance in Anopheles gambiae), signaling through IMD, FADD, and the caspase Dredd to cleave and activate the NF-κB factor Relish (REL2 in mosquitoes), which drives transcription of Diptericin, Attacin, Cecropin, and the complement-like thioester protein TEP1. Within 6 to 12 hours of septic injury, a single insect fat body secretes antimicrobial peptides into the hemolymph at micromolar concentrations (10–100 μM) sufficient to lyse invading bacteria systemically.

1. Lemaitre, B., Nicolas, E., Michaut, L., Reichhart, J.-M., & Hoffmann, J. A. (1996). "The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults." Cell, 86(6), 973–983. https://doi.org/10.1016/S0092-8674(00)80172-580172-5)
2. Burmester, T. (1999). "Evolution and function of the insect hexamerins." European Journal of Entomology, 96(3), 213–225. https://www.eje.cz/artkey/eje-199903-0001.php
3. Grönke, S., Mildner, A., Fellert, S., Tennagels, N., Petry, S., Müller, G., Jäckle, H., & Kühnlein, R. P. (2005). "Brummer lipase is an evolutionary conserved fat storage regulator in Drosophila." Cell Metabolism, 1(5), 323–330. https://doi.org/10.1016/j.cmet.2005.04.003
4. Arrese, E. L., & Soulages, J. L. (2010). "Insect fat body: energy, metabolism, and regulation." Annual Review of Entomology, 55, 207–225. https://doi.org/10.1146/annurev-ento-112408-085356
5. Li, S., Yu, X., & Feng, Q. (2019). "Fat body biology in the last decade." Annual Review of Entomology, 64, 315–333. https://doi.org/10.1146/annurev-ento-011118-112007