Garcia 2020 Mol Hum Reprod

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Publications in the MiPMap
Garcia BM, Machado TS, Carvalho KF, Nolasco P, Nociti RP, Del Collado M, Capo Bianco MJD, Grejo MP, Neto JDA, Sugiyama FHC, Tostes K, Pandey AK, Gonçalves LM, Perecin F, Meirelles FV, Ferraz JBS, Vanzela EC, Boschero AC, Guimarães FEG, Abdulkader F, Laurindo FRM, Kowaltowski AJ, Chiaratti MR (2020) Mice born to females with oocyte-specific deletion of mitofusin 2 have increased weight gain and impaired glucose homeostasis. Mol Hum Reprod 26:938-52.

Β» PMID: 33118034 Open Access

Garcia Bruna M, Machado Thiago S, Carvalho Karen F, Nolasco Patricia, Nociti Ricardo P, Del Collado Maite, Capo Bianco Maria J D, Grejo Mateus P, Neto Jose Djaci Augusto, Sugiyama Fabricia H C, Tostes Katiane, Pandey Anand K, Goncalves Luciana M, Perecin Felipe, Meirelles Flavio V, Ferraz Jose Bento S, Vanzela Emerielle C, Boschero Antonio C, Guimaraes Francisco E G, Abdulkader Fernando, Laurindo Francisco R M, Kowaltowski Alicia J, Chiaratti Marcos R (2020) Mol Hum Reprod

Abstract: Offspring born to obese and diabetic mothers are prone to metabolic diseases, a phenotype that has been linked to mitochondrial dysfunction and endoplasmic reticulum [ER] stress in oocytes. In addition, metabolic diseases impact the architecture and function of mitochondria-ER contact sites [MERCs], changes which associate with mitofusin 2 [MFN2] repression in muscle, liver and hypothalamic neurons. MFN2 is a potent modulator of mitochondrial metabolism and insulin signaling, with a key role in mitochondrial dynamics and tethering with the ER. Here, we investigated whether offspring born to mice with MFN2-deficient oocytes are prone to obesity and diabetes. Deletion of Mfn2 in oocytes resulted in a profound transcriptomic change, with evidence of impaired mitochondrial and ER function. Moreover, offspring born to females with oocyte-specific deletion of Mfn2 presented increased weight gain and glucose intolerance. This abnormal phenotype was linked to decreased insulinemia and defective insulin signaling, but not mitochondrial and ER defects in offspring liver and skeletal muscle. In conclusion, this study suggests a link between disrupted mitochondrial/ER function in oocytes and increased risk of metabolic diseases in the progeny. Future studies should determine whether MERC architecture and function are altered in oocytes from obese females, which might contribute toward transgenerational transmission of metabolic diseases. β€’ Keywords: MERC, MFN2, Diabetes, Endoplasmic reticulum, Metabolic diseases, Mitochondria, Mitochondria dynamics, mtDNA, Obesity, Oocyte β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: BR Sao Paulo Kowaltowski AJ

Labels: MiParea: Respiration, Genetic knockout;overexpression, Developmental biology  Pathology: Diabetes, Obesity 

Organism: Mouse  Tissue;cell: Liver  Preparation: Isolated mitochondria 

Coupling state: LEAK, OXPHOS, ET  Pathway:HRR: Oxygraph-2k 


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