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
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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