A MicroRNA Linking Human Positive Selection and Metabolic Disorders
Wang L, Sinnott-Armstrong N, Wagschal A, Wark AR, Camporez JP, Perry RJ, Ji F, Sohn Y, Oh J, Wu S, Chery J, Moud BN, Saadat A, Dankel SN, Mellgren G, Tallapragada DSP, Strobel SM, Lee MJ, Tewhey R, Sabeti PC, Schaefer A, Petri A, Kauppinen S, Chung RT, Soukas A, Avruch J, Fried SK, Hauner H, Sadreyev RI, Shulman GI, Claussnitzer M, Näär AM. A MicroRNA Linking Human Positive Selection and Metabolic Disorders. Cell 2020, 183: 684-701.e14. PMID: 33058756, PMCID: PMC8092355, DOI: 10.1016/j.cell.2020.09.017.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytes, BrownAdiposityAllelesAnimalsCell DifferentiationCell LineCells, CulturedDiet, High-FatEnergy MetabolismEpigenesis, GeneticGenetic LociGlucoseHomeostasisHumansHypertrophyInsulin ResistanceLeptinMaleMammalsMetabolic DiseasesMice, Inbred C57BLMice, ObeseMicroRNAsObesityOligonucleotidesSpecies SpecificityConceptsPositive selectionMiR-128Additional genetic elementsCrucial metabolic regulatorAncient adaptationEvolutionary adaptationGenetic elementsMetabolic regulatorGenetic ablationLociMetabolic maladaptationLactase geneAntisense targetingMetabolic disease modelsThrifty phenotypeDisease modelsDiet-induced obesityMetabolic diseasesAbility of adultsMammalsAdaptationGenesMicroRNAsRegulatorSelectionObesity-Linked PPARγ S273 Phosphorylation Promotes Insulin Resistance through Growth Differentiation Factor 3
Hall JA, Ramachandran D, Roh HC, DiSpirito JR, Belchior T, Zushin PH, Palmer C, Hong S, Mina AI, Liu B, Deng Z, Aryal P, Jacobs C, Tenen D, Brown CW, Charles JF, Shulman GI, Kahn BB, Tsai LTY, Rosen ED, Spiegelman BM, Banks AS. Obesity-Linked PPARγ S273 Phosphorylation Promotes Insulin Resistance through Growth Differentiation Factor 3. Cell Metabolism 2020, 32: 665-675.e6. PMID: 32941798, PMCID: PMC7543662, DOI: 10.1016/j.cmet.2020.08.016.Peer-Reviewed Original ResearchConceptsInsulin resistanceInsulin sensitivitySide effectsObesity-linked phosphorylationSignificant side effectsLigands of PPARγHyperinsulinemic-euglycemic clamp experimentsPromotes Insulin ResistanceDiabetogenic roleReceptor agonismGrowth differentiation factor 3Healthy miceBody weightMice revealsThiazolidinedionesClamp experimentsPPARγMiceInhibits BMPFamily membersFactor 3Putative targetsSerine 273Ectopic expressionBMP family membersSlc20a1/Pit1 and Slc20a2/Pit2 are essential for normal skeletal myofiber function and survival
Chande S, Caballero D, Ho BB, Fetene J, Serna J, Pesta D, Nasiri A, Jurczak M, Chavkin NW, Hernando N, Giachelli CM, Wagner CA, Zeiss C, Shulman GI, Bergwitz C. Slc20a1/Pit1 and Slc20a2/Pit2 are essential for normal skeletal myofiber function and survival. Scientific Reports 2020, 10: 3069. PMID: 32080237, PMCID: PMC7033257, DOI: 10.1038/s41598-020-59430-4.Peer-Reviewed Original ResearchConceptsHyp miceMuscle functionSkeletal muscleMyofiber functionNormal body weightSkeletal muscle atrophyGene dose-dependent reductionConditional knockout miceReduced oxygen consumption rateStimulation of AMP kinaseKnockout miceHypophosphatemic disordersMuscle atrophyERK1/2 activationGrip strengthConditional deletionHormonal changesLow bloodBody weightC2C12 myoblastsMiceFurther evaluationBlood phosphateDependent reductionAMP kinase