RT Journal Article
T1 Adipose tissue depot-specific intracellular and extracellular cues contributing to insulin resistance in obese individuals.
A1 Guzman-Ruiz, Rocio
A1 Tercero-Alcazar, Carmen
A1 Rabanal-Ruiz, Yoana
A1 Diaz-Ruiz, Alberto
A1 El Bekay, Rajaa
A1 Rangel-Zuñiga, Oriol A
A1 Navarro-Ruiz, M Carmen
A1 Molero, Laura
A1 Membrives, Antonio
A1 Ruiz-Rabelo, Juan F
A1 Pandit, Abhay
A1 Lopez-Miranda, Jose
A1 Tinahones, Francisco J
A1 Malagon, Maria M
K1 3D culture
K1 Adipocytes
K1 Extracellular matrix
K1 Lipid droplets
AB Adipose tissue dysregulation in obesity strongly influences systemic metabolic homeostasis and is often linked to insulin resistance (IR). However, the molecular mechanisms underlying adipose tissue dysfunction in obesity are not fully understood. Herein, a proteomic analysis of subcutaneous (SC) and omental (OM) fat from lean subjects and obese individuals with different degrees of insulin sensitivity was performed to identify adipose tissue biomarkers related to obesity-associated metabolic disease. Our results suggest that dysregulation of both adipose tissue extracellular matrix (ECM) organization and intracellular trafficking processes may be associated with IR in obesity. Thus, abnormal accumulation of the small leucine-rich proteoglycan, lumican, as observed in SC fat of IR obese individuals, modifies collagen I organization, impairs adipogenesis and activates stress processes [endoplasmic reticulum and oxidative stress] in adipocytes. In OM fat, IR is associated with increased levels of the negative regulator of the Rab family of small GTPases, GDI2, which alters lipid storage in adipocytes by inhibiting insulin-stimulated binding of the Rab protein, Rab18, to lipid droplets. Together, these results indicate that lumican and GDI2 might play depot-dependent, pathogenic roles in obesity-associated IR. Our findings provide novel insights into the differential maladaptive responses of SC and OM adipose tissue linking obesity to IR.
PB Wiley
YR 2020
FD 2020-04-22
LK http://hdl.handle.net/10668/15375
UL http://hdl.handle.net/10668/15375
LA en
NO Guzmán-Ruiz R, Tercero-Alcázar C, Rabanal-Ruiz Y, Díaz-Ruiz A, El Bekay R, Rangel-Zuñiga OA, et al. Adipose tissue depot-specific intracellular and extracellular cues contributing to insulin resistance in obese individuals. FASEB J. 2020 Jun;34(6):7520-7539
DS RISalud
RD Apr 17, 2025