title: Short-chain fatty acid propionate alleviates Akt2 knockout-induced myocardial contractile dysfunction.
abstract: BACKGROUND AND AIMS. Dysregulation of Akt has been implicated in diseases such as cancer and diabetes, although little is known about the role of Akt deficiency on cardiomyocyte contractile function. This study was designed to examine the effect of Akt2 knockout-induced cardiomyocyte contractile response and the effect of dietary supplementation of short-chain fatty acid propionate on Akt2 knockout-induced cardiac dysfunction, if any. METHODS AND RESULTS. Adult male wild-type (WT) and Akt2 knockout mice were treated with propionate (0.3 g/kg, p.o.) or vehicle for 7 days. Oral glucose tolerance test (OGTT) was performed. Cardiomyocyte contractile function and mitochondrial membrane potential were assessed. Expression of insulin-signaling molecules Akt, PTEN, GSK3β, and eNOS receptors for short-chain fatty acids GPR41, and GPR43 as well as protein phosphatase PP2AA, PP2AB, PP2C were evaluated using Western blot analysis. Our results revealed that Akt2 knockout led to overt glucose intolerance, compromised cardiomyocyte contractile function (reduced peak shortening and maximal velocity of shortening/relengthening as well as prolonged relengthening), loss of mitochondrial membrane potential, decreased GPR41 and elevated GPR43 expression, all of which, with the exception of glucose intolerance and elevated GPR43 level, were significantly attenuated by propionate. Neither Akt2 knockout nor propionate affected the expression of protein phosphatases, eNOS, pan, and phosphorylated PTEN and GSK3β. CONCLUSIONS. Taken together, these data depicted that Akt2 knockout may elicit cardiomyocyte contractile and mitochondrial defects and a beneficial role of propionate or short-chain fatty acids against Akt2 deficiency-induced cardiac anomalies.
authors.affiliation: Department of Pharmacology, Xinjiang Medical University, Urumqi, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Li
authors.forename: Yinan
authors.initials: Y
authors.lastname: Hua
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
mesh_terms: D000818:Animals; D019587:Dietary Supplements; D018149:Glucose Intolerance / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C506481:Ffar2 protein, mouse; C506482:Gpcr41 protein, mouse; D007328:Insulin; D011422:Propionates; D043562:Receptors, G-Protein-Coupled; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; C494922:Akt2 protein, mouse; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; C029658:propionic acid