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      What fuels the fly: Energy metabolism in Drosophila and its application to the study of obesity and diabetes

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          Abstract

          Drosophila is a useful model system to study the regulation of energy metabolism and its diseases like obesity and diabetes.

          Abstract

          The organs and metabolic pathways involved in energy metabolism, and the process of ATP production from nutrients, are comparable between humans and Drosophila melanogaster. This level of conservation, together with the power of Drosophila genetics, makes the fly a very useful model system to study energy homeostasis. Here, we discuss the major organs involved in energy metabolism in Drosophila and how they metabolize different dietary nutrients to generate adenosine triphosphate. Energy metabolism in these organs is controlled by cell-intrinsic, paracrine, and endocrine signals that are similar between Drosophila and mammals. We describe how these signaling pathways are regulated by several physiological and environmental cues to accommodate tissue-, age-, and environment-specific differences in energy demand. Last, we discuss several genetic and diet-induced fly models of obesity and diabetes that can be leveraged to better understand the molecular basis of these metabolic diseases and thereby promote the development of novel therapies.

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          Most cited references163

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          mTOR Signaling in Growth, Metabolism, and Disease.

          The mechanistic target of rapamycin (mTOR) coordinates eukaryotic cell growth and metabolism with environmental inputs, including nutrients and growth factors. Extensive research over the past two decades has established a central role for mTOR in regulating many fundamental cell processes, from protein synthesis to autophagy, and deregulated mTOR signaling is implicated in the progression of cancer and diabetes, as well as the aging process. Here, we review recent advances in our understanding of mTOR function, regulation, and importance in mammalian physiology. We also highlight how the mTOR signaling network contributes to human disease and discuss the current and future prospects for therapeutically targeting mTOR in the clinic.
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            mTOR Signaling in Growth, Metabolism, and Disease.

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              Drosophila microbiome modulates host developmental and metabolic homeostasis via insulin signaling.

              The symbiotic microbiota profoundly affect many aspects of host physiology; however, the molecular mechanisms underlying host-microbe cross-talk are largely unknown. Here, we show that the pyrroloquinoline quinone-dependent alcohol dehydrogenase (PQQ-ADH) activity of a commensal bacterium, Acetobacter pomorum, modulates insulin/insulin-like growth factor signaling (IIS) in Drosophila to regulate host homeostatic programs controlling developmental rate, body size, energy metabolism, and intestinal stem cell activity. Germ-free animals monoassociated with PQQ-ADH mutant bacteria displayed severe deregulation of developmental and metabolic homeostasis. Importantly, these defects were reversed by enhancing host IIS or by supplementing the diet with acetic acid, the metabolic product of PQQ-ADH.
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                Author and article information

                Journal
                Sci Adv
                Sci Adv
                SciAdv
                advances
                Science Advances
                American Association for the Advancement of Science
                2375-2548
                June 2021
                09 June 2021
                : 7
                : 24
                : eabg4336
                Affiliations
                [1 ]Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
                [2 ]Howard Hughes Medical Institute, Boston, MA 02115, USA.
                Author notes
                Author information
                http://orcid.org/0000-0003-0613-7916
                http://orcid.org/0000-0001-7542-472X
                Article
                abg4336
                10.1126/sciadv.abg4336
                8189582
                34108216
                fc3ae71f-389a-47a2-a2d4-d0d51332c981
                Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

                History
                : 06 January 2021
                : 23 April 2021
                Funding
                Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: 5P01CA120964
                Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01AR057352
                Funded by: doi http://dx.doi.org/10.13039/100000011, Howard Hughes Medical Institute;
                Award ID: N/A
                Funded by: doi http://dx.doi.org/10.13039/100000011, Howard Hughes Medical Institute;
                Funded by: Perrimon Lab;
                Award ID: 5P01CA120964
                Funded by: Perrimon Lab;
                Award ID: R01AR057352
                Categories
                Review
                Reviews
                SciAdv reviews
                Genetics
                Genetics
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