TY - JOUR
T1 - Development of diet-induced insulin resistance in adult Drosophila melanogaster
AU - Morris, Siti Nur Sarah
AU - Coogan, Claire
AU - Chamseddin, Khalil
AU - Fernandez-Kim, Sun Ok
AU - Kolli, Santharam
AU - Keller, Jeffrey N.
AU - Bauer, Johannes H.
N1 - Funding Information:
The authors would like to thank B. Edgar for the kind gift of fly stocks. We also thank Chris Thephachanh for technical assistance. This work was supported NIA AG029723 to JHB and Hamilton Undergraduate Research Awards to CC and KHC. JHB is a recipient of the Ralph. E. Powe Junior Faculty Enhancement Award.
PY - 2012/8
Y1 - 2012/8
N2 - The fruit fly Drosophila melanogaster is increasingly utilized as an alternative to costly rodent models to study human diseases. Fly models exist for a wide variety of human conditions, such as Alzheimer's and Parkinson's Disease, or cardiac function. Advantages of the fly system are its rapid generation time and its low cost. However, the greatest strength of the fly system are the powerful genetic tools that allow for rapid dissection of molecular disease mechanisms. Here, we describe the diet-dependent development of metabolic phenotypes in adult fruit flies. Depending on the specific type of nutrient, as well as its relative quantity in the diet, flies show weight gain and changes in the levels of storage macromolecules. Furthermore, the activity of insulin-signaling in the major metabolic organ of the fly, the fat body, decreases upon overfeeding. This decrease in insulin-signaling activity in overfed flies is moreover observed when flies are challenged with an acute food stimulus, suggesting that overfeeding leads to insulin resistance. Similar changes were observed in aging flies, with the development of the insulin resistance-like phenotype beginning at early middle ages. Taken together, these data demonstrate that imbalanced diet disrupts metabolic homeostasis in adult . D. melanogaster and promotes insulin-resistant phenotypes. Therefore, the fly system may be a useful alternative tool in the investigation of molecular mechanisms of insulin resistance and the development of pharmacologic treatment options.
AB - The fruit fly Drosophila melanogaster is increasingly utilized as an alternative to costly rodent models to study human diseases. Fly models exist for a wide variety of human conditions, such as Alzheimer's and Parkinson's Disease, or cardiac function. Advantages of the fly system are its rapid generation time and its low cost. However, the greatest strength of the fly system are the powerful genetic tools that allow for rapid dissection of molecular disease mechanisms. Here, we describe the diet-dependent development of metabolic phenotypes in adult fruit flies. Depending on the specific type of nutrient, as well as its relative quantity in the diet, flies show weight gain and changes in the levels of storage macromolecules. Furthermore, the activity of insulin-signaling in the major metabolic organ of the fly, the fat body, decreases upon overfeeding. This decrease in insulin-signaling activity in overfed flies is moreover observed when flies are challenged with an acute food stimulus, suggesting that overfeeding leads to insulin resistance. Similar changes were observed in aging flies, with the development of the insulin resistance-like phenotype beginning at early middle ages. Taken together, these data demonstrate that imbalanced diet disrupts metabolic homeostasis in adult . D. melanogaster and promotes insulin-resistant phenotypes. Therefore, the fly system may be a useful alternative tool in the investigation of molecular mechanisms of insulin resistance and the development of pharmacologic treatment options.
KW - Diabetes
KW - Diet
KW - Drosophila melanogaster
KW - Insulin resistance
KW - Insulin signaling
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U2 - 10.1016/j.bbadis.2012.04.012
DO - 10.1016/j.bbadis.2012.04.012
M3 - Article
C2 - 22542511
AN - SCOPUS:84861390529
SN - 0925-4439
VL - 1822
SP - 1230
EP - 1237
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 8
ER -