# The roles of miR-155 in regulating atherosclerosis and metabolically healthy obesity

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $660,657

## Abstract

Title: MiR-155 differentially regulates atherosclerosis and metabolically healthy obesity
 According to the Centers for Disease Control and Prevention, the prevalence of obesity (Ob) has
increased to over 35% of the U.S. adult population, or more than 85 million adults
(https://www.cdc.gov/obesity/data/adult.html). Ob is an important risk factor for type 2 diabetes mellitus
(T2DM), various cancers, nonalcoholic fatty liver disease (NAFLD); cardiovascular disease (CVD), and
mortality. In contrast to the classical Ob associated CVD (COB), evidence has shown that some obese
individuals are metabolically healthy, termed metabolically healthy obesity (MHO) , and counts for 18-44% of
obese adults and 10% adult population. Unlike COB, MHO reports less incidence of atherosclerosis, no insulin
resistance (IR) but Ob. MHO is not truly “healthy” since MHO significantly increase incidences of T2DM,
hypertension, and metabolic syndrome (MetS). Therefore, novel therapies are urgently needed to inhibit MHO
transition to COB. However, the mechanisms underlying MHO transition to COB remain poorly characterized
due to lack of appropriate animal models for MHO transition to COB. The goal of this project is to determine
the underlying mechanisms and establish new models of MHO transition to COB.
 We have long-standing interest in studying metabolic CVD and published many papers on endothelial
cell (EC) activation, EC dysfunction, VSMC phenotypic switching, monocyte (MC)/macrophage (M)
recruitment, Foxp3+ Treg in inhibiting CV inflammation, atherosclerosis, Ob/diabetes, chronic kidney disease
(CKD), and the roles of caspase-1(Casp1)/inflammmasome in CVD. Therefore, we have sufficient expertise in
carrying out this proposal. Our strong preliminary data, new publications showed that: 1) miR155 is
significantly upregulated in atherosclerosis aorta and in TNFα-, IL-1β- and lipopolysaccharide (LPS)-stimulated
aortic EC; 2) miR155-/-/ApoE-/- mice (DKO) have decreased atherosclerosis, but increase high fat diet (HF)-
induced white adipose tissue (WAT) hypertrophy; 3) miR155 KO M produce less TNFα and IL-1β as others
reported; 4) HF significantly increased DKO WAT M (ATM), proinflammatory adipokines resistin and leptin,
which creates systemic proinflammatory conditions and promote MHO transition to COB. These findings
suggest that a single cell type, miR155-/- M, in two different tissue contexts (aorta and WAT), regulates MHO;
5) DKO have no IR and no glucose intolerance, suggesting a MHO status; and 6) we obtained miR155fl/fl mice
and are generating cell-specific miR155-/- mice. Our data/publications strongly suggest that DKO have
decreased atherosclerosis but have increased HF-induced Ob and ATM without IR, which make DKO as the
first model for studying MHO transition to COB. Therefore, the central to be tested is that
extended HF feeding transitions MHO to COB by increasing adipose tissue inflammation via increased
saturated fatty acids (SFA)-/proinflammatory adipokin...

## Key facts

- **NIH application ID:** 9938613
- **Project number:** 5R01HL138749-04
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Xiaofeng Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $660,657
- **Award type:** 5
- **Project period:** 2017-07-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938613

## Citation

> US National Institutes of Health, RePORTER application 9938613, The roles of miR-155 in regulating atherosclerosis and metabolically healthy obesity (5R01HL138749-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9938613. Licensed CC0.

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