Ileal interposition surgery targets the hepatic TGF-β pathway, influencing gluconeogenesis and mitochondrial bioenergetics in the UCD-T2DM rat model of diabetes
Autor: | James L. Graham, Connie Hung, Eleonora Napoli, Pascal Froment, Peter J. Havel, Catherine Ross-Inta, Kimber L. Stanhope, Amanda L. Flores-Torres, Cecilia R Giulivi |
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Přispěvatelé: | University of California [Davis] (UC Davis), University of California, Department of Nutrition, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS) |
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Blood Glucose Male type 2 diabetes mellitus Physiology receptor [SDV]Life Sciences [q-bio] Medical Physiology Smad Proteins SMAD Biochemistry Rats Sprague-Dawley Phosphatidylinositol 3-Kinases 0302 clinical medicine Intestinal mucosa Glucagon-Like Peptide 1 Transforming Growth Factor beta glyceroneogenesis IT surgery 2.1 Biological and endogenous factors Medicine Insulin digested nutrients Aetiology Liver Disease Diabetes metabolomics 3. Good health Mitochondria Liver Lipogenesis Mothers against decapentaplegic Type 2 Biotechnology Signal Transduction biliary Biochemistry & Molecular Biology medicine.medical_specialty Metabolic and Endocrine Diabetes Mellitus Experimental Experimental 03 medical and health sciences Oral and Gastrointestinal Ileum Diabetes Mellitus Genetics Glyceroneogenesis Animals [INFO]Computer Science [cs] Obesity Molecular Biology Nutrition Animal business.industry Research Gluconeogenesis Lipid Metabolism Surgery Rats Metabolic pathway Disease Models Animal 030104 developmental biology Glucose gluconeogenesis Diabetes Mellitus Type 2 Disease Models Hepatic stellate cell Sprague-Dawley Biochemistry and Cell Biology Digestive Diseases business Energy Metabolism 030217 neurology & neurosurgery |
Zdroj: | FASEB Journal FASEB Journal, Federation of American Society of Experimental Biology, 2019, 33 (10), pp.11270-11283. ⟨10.1096/fj.201802714R⟩ FASEB J FASEB journal : official publication of the Federation of American Societies for Experimental Biology, vol 33, iss 10 |
ISSN: | 0892-6638 1530-6860 |
Popis: | International audience; Ileal interposition (IT) is a surgical procedure that increases the delivery of incompletely digested nutrients and biliary and pancreatic secretions to the distal intestinal mucosa. Here, we investigated the metabolic impact of this intervention in 2-mo-old prediabetic University of California, Davis type 2 diabetes mellitus rats by assessing liver gene expression at 1.5 mo post-IT surgery. Pathway analysis indicated decreased signaling via TGF-β/Smad (a family of proteins named mothers against decapentaplegic homologs), peroxisome proliferator-activated receptor (PPAR), and PI3K-Akt-AMPK–mechanistic target of rapamycin, likely targeting hepatic stellate cells because differentiation and activation of these cells is associated with decreased signaling via PPAR and TGF-β/Smad. IT surgery up-regulated the expression of genes involved in regulation of cholesterol and terpenoid syntheses and down-regulated those involved in glycerophospholipid metabolism [including cardiolipin (CL)], lipogenesis, and gluconeogenesis. Consistent with the down-regulation of the hepatic CL pathway, IT surgery produced a metabolic switch in liver, kidney cortex, and fat depots toward decreased mitochondrial fatty acid β-oxidation, the process required to fuel high energy–demanding pathways (e.g., gluconeogenesis and glyceroneogenesis), whereas opposite effects were observed in skeletal and cardiac muscles. This study demonstrates for the first time the presence of metabolic pathways that complement the effects of IT surgery to maximize its benefits and potentially identify similarly effective, durable, and less invasive therapeutic options for metabolic disease, including inhibitors of TGF-β signaling.—Hung, C., Napoli, E., Ross-Inta, C., Graham, J., Flores-Torres, A. L., Stanhope, K. L., Froment, P., Havel, P. J., Giulivi, C. Ileal interposition surgery targets the hepatic TGF-β pathway, influencing gluconeogenesis and mitochondrial bioenergetics in the UCD-T2DM rat model of diabetes. |
Databáze: | OpenAIRE |
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