TY - JOUR
T1 - Increased expression of resistin in MicroRNA-155-deficient white adipose tissues may be a possible driver of metabolically healthy obesity transition to classical obesity
AU - Johnson, Candice
AU - Drummer, Charles
AU - Virtue, Anthony
AU - Gao, Tracy
AU - Wu, Susu
AU - Hernandez, Miguel
AU - Singh, Lexy
AU - Wang, Hong
AU - Yang, Xiao Feng
N1 - Publisher Copyright:
Copyright © 2018 Johnson, Drummer, Virtue, Gao, Wu, Hernandez, Singh, Wang and Yang.
PY - 2018/10/12
Y1 - 2018/10/12
N2 - We reported that microRNA-155 (miR-155) deficiency in ApoE-/- mice yields a novel metabolically healthy obese (MHO) model, which exhibits improved atherosclerosis but results in obesity, non-alcoholic fatty liver disease (NAFLD) without insulin resistance. Using experimental data mining approaches combined with experiments, we found that, among 109 miRNAs, miR-155, and miR-221 are significantly modulated in all four hyperlipidemia-related diseases (HRDs), namely atherosclerosis, NAFLD, obesity and type II diabetes (T2DM). MiR-155 is significantly upregulated in atherosclerosis and decreased in other HRDs. MiR-221 is increased in three HRDs but reduced in obesity. These findings led to our new classification of types I and II MHOs, which are regulated by miR-221 and miR-155, respectively. Western blots showed that the proinflammatory adipokine, resistin, is significantly increased in white adipose tissues (WAT) of the MHO mice, revealing our newly proposed, miR-155-suppressed “secondary wave inflammatory state (SWIS),” characteristic of MHO transition to classical obesity (CO). Taken together, we are first to show that MHO may have heterogeneity in comorbidities, and is therefore classified into type I, and type II MHOs; and that increased expression of resistin in miR-155-/- white adipose tissues may be a driver for SWIS in MHO transition to CO. Our findings provide novel insights into the pathogenesis of MHO, MHO transition to CO, hyperlipidemic pathways related to cancer, and new therapeutic targets.
AB - We reported that microRNA-155 (miR-155) deficiency in ApoE-/- mice yields a novel metabolically healthy obese (MHO) model, which exhibits improved atherosclerosis but results in obesity, non-alcoholic fatty liver disease (NAFLD) without insulin resistance. Using experimental data mining approaches combined with experiments, we found that, among 109 miRNAs, miR-155, and miR-221 are significantly modulated in all four hyperlipidemia-related diseases (HRDs), namely atherosclerosis, NAFLD, obesity and type II diabetes (T2DM). MiR-155 is significantly upregulated in atherosclerosis and decreased in other HRDs. MiR-221 is increased in three HRDs but reduced in obesity. These findings led to our new classification of types I and II MHOs, which are regulated by miR-221 and miR-155, respectively. Western blots showed that the proinflammatory adipokine, resistin, is significantly increased in white adipose tissues (WAT) of the MHO mice, revealing our newly proposed, miR-155-suppressed “secondary wave inflammatory state (SWIS),” characteristic of MHO transition to classical obesity (CO). Taken together, we are first to show that MHO may have heterogeneity in comorbidities, and is therefore classified into type I, and type II MHOs; and that increased expression of resistin in miR-155-/- white adipose tissues may be a driver for SWIS in MHO transition to CO. Our findings provide novel insights into the pathogenesis of MHO, MHO transition to CO, hyperlipidemic pathways related to cancer, and new therapeutic targets.
KW - Atherosclerosis
KW - Diabetes
KW - Fatty liver disease
KW - MiR-155
KW - MiR-221
KW - MicroRNAs
KW - Obesity
KW - Resistin
UR - http://www.scopus.com/inward/record.url?scp=85055099632&partnerID=8YFLogxK
U2 - 10.3389/fphys.2018.01297
DO - 10.3389/fphys.2018.01297
M3 - Article
AN - SCOPUS:85055099632
SN - 1664-042X
VL - 9
JO - Frontiers in Physiology
JF - Frontiers in Physiology
IS - OCT
M1 - 1297
ER -