title: Ectopic lipid accumulation: A potential cause for metabolic disturbances and a contributor to the alteration of kidney function.
abstract: Ectopic lipid accumulation is now known to be a mechanism that contributes to organ injury in the context of metabolic diseases. In muscle and liver, accumulation of lipids impairs insulin signaling. This hypothesis accounts for the mechanism of insulin resistance in obesity, type 2 diabetes, aging and lipodystrophy. Increasing data suggest that lipid accumulation in the kidneys could also contribute to the alteration of kidney function in the context of metabolic syndrome and obesity. Furthermore and more unexpectedly, animal models of kidney disease exhibit a decreased adiposity and ectopic lipid redistribution suggesting that kidney disease may be a state of lipodystrophy. However, whether this abnormal lipid partitioning during chronic kidney disease (CKD) may have any functional impact in these tissues needs to be investigated. Here, we provide a perspective by defining the problem and analyzing the possible causes and consequences. Further human studies are required to strengthen these observations, and provide novel therapeutic approaches.
authors.affiliation: Université de Lyon, INSERM U1060, CarMeN, INSA de Lyon, Univ Lyon-1, F-69621 Villeurbanne, France; Hospices Civils de Lyon, Department of Nephrology, Hôpital E Herriot, Lyon F-69003, France. Electronic address: fitsum.guebre-egziabher@chu-lyon.fr.
authors.forename: Fitsum
authors.initials: F
authors.lastname: Guebre-Egziabher
authors.forename: Pascaline M
authors.initials: PM
authors.lastname: Alix
authors.forename: Laetitia
authors.initials: L
authors.lastname: Koppe
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Pelletier
authors.forename: Emilie
authors.initials: E
authors.lastname: Kalbacher
authors.forename: Denis
authors.initials: D
authors.lastname: Fouque
authors.forename: Christophe O
authors.initials: CO
authors.lastname: Soulage
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D004075:Diglycerides / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism / Q000235:genetics*; D008060:Lipodystrophy / Q000378:metabolism / Q000473:pathology*; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D051436:Renal Insufficiency, Chronic / Q000378:metabolism / Q000473:pathology
chemical_list: D004075:Diglycerides; D005227:Fatty Acids; D007328:Insulin
keywords: ACC; AMP-activated protein kinase; AMPK; ATMs; BMI; C/EBP-α; CCAAT/enhancer binding protein alpha; CKD; CPT-1; ChREBP; Chronic kidney disease; DAG; DN; Diacylglycerols; ER; FA; FA-coA; FABP-4; FAS; FSP27; GLUT-4; HOMA-IR; IKK-β; IRS-1/2; Insulin resistance; JNK; LPS; Lipodystrophy; Lipotoxicity; MMPC; Met-S; NAFLD; NEFA; NFκB; PAMPs; PKB/Akt; PKC-ε; PKC-θ; PPAR-αperoxisome; PPAR-γperoxisome; ROS; SFA; SREBP-1; TLR-2; TLR-4; Toll-like receptor 2; Toll-like receptor 4; UPR; WAT; acetyl-coA carboxylase; adipose tissue macrophages; body mass index; c-jun N-terminal kinase; carbohydrate response element binding protein; carnitine palmitoyl transferase-1; chronic kidney disease; diabetic nephropathy; diacylglycerols; endoplasmic reticulum; fat specific protein 27; fatty acid binding protein-4; fatty acid synthase; fatty acids; fatty acyl-Co-enzyme A; glucose transporter type 4; homeostatic model assessment of insulin resistance; inhibitor of nuclear factor kappa-B kinase beta; insulin receptor substrates 1 and 2; lipopolysaccharide; metabolic syndrome; multipotent mesenchymal progenitor cells; non-alcoholic fatty liver disease; non-esterified fatty acids; nuclear factor kappa-B; pathogen-associated molecular patterns; proliferator-activated receptor alpha; proliferator-activated receptor gamma; protein kinase B/Akt; protein kinase C epsilon; protein kinase C theta; reactive oxygen species; saturated fatty acids; sterol regulatory element binding protein-1; unfolded protein response; white adipose tissue