Role of fat body lipogenesis in protection against the effects of caloric overload in Drosophila.
The Drosophila fat body is a liver- and adipose-like tissue that stores fat and serves as a detoxifying and immune responsive organ. We have previously shown that a high sugar diet leads to elevated hemolymph glucose and systemic insulin resistance in developing larvae and adults. Here, we used stable isotope tracer feeding to demonstrate that rearing larvae on high sugar diets impaired the synthesis of esterified fatty acids from dietary glucose. Fat body lipid profiling revealed changes in both carbon chain length and degree of unsaturation of fatty acid substituents, particularly in stored triglycerides. We tested the role of the fat body in larval tolerance of caloric excess. Our experiments demonstrated that lipogenesis was necessary for animals to tolerate high sugar feeding as tissue-specific loss of orthologs of carbohydrate response element-binding protein or stearoyl-CoA desaturase 1 resulted in lethality on high sugar diets. By contrast, increasing the fat content of the fat body by knockdown of king-tubby was associated with reduced hyperglycemia and improved growth and tolerance of high sugar diets. Our work supports a critical role for the fat body and the Drosophila carbohydrate response element-binding protein ortholog in metabolic homeostasis in Drosophila.
Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Laura Palanker
LP
Musselman
Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Jill L
JL
Fink
Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Prasanna Venkatesh
PV
Ramachandran
Division of Geriatrics and Nutritional Sciences, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Bruce W
BW
Patterson
Division of Geriatrics and Nutritional Sciences, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Adewole L
AL
Okunade
Department of Computer Science and Center for Genome Sciences and Systems Biology, Washington University, St. Louis, Missouri 63130.
Ezekiel
E
Maier
Department of Computer Science and Center for Genome Sciences and Systems Biology, Washington University, St. Louis, Missouri 63130.
Michael R
MR
Brent
Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
John
J
Turk
Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110. Electronic address: tbaransk@dom.wustl.edu.
Thomas J
TJ
Baranski
D000818:Animals; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D002149:Energy Intake; D004734:Energy Metabolism; D005216:Fat Body / Q000378:metabolism* / Q000502:physiology; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006458:Hemolymph / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism; D007659:Ketones / Q000378:metabolism; D007814:Larva / Q000378:metabolism; D050155:Lipogenesis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D059467:Transcriptome
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D005227:Fatty Acids; D007659:Ketones; D009687:Nuclear Proteins; D010743:Phospholipids; C484002:mio protein, Drosophila; D044943:Fatty Acid Desaturases; C408225:desat1 protein, Drosophila; D005947:Glucose