A Medium Chain Fatty Acid, 6-hydroxyhexanoic acid (6-HHA), Protects Against Obesity and Insulin Resistance

Sara C. Sebag; Qingwen Qian; Chawin Upara; Qiong Ding; Huojun Cao; Liu Hong; Ling Yang

doi:10.1101/2023.07.19.549684

Back

A Medium Chain Fatty Acid, 6-hydroxyhexanoic acid (6-HHA), Protects Against Obesity and Insulin Resistance

Preprint

Open access

A Medium Chain Fatty Acid, 6-hydroxyhexanoic acid (6-HHA), Protects Against Obesity and Insulin Resistance

Sara C. Sebag, Qingwen Qian, Chawin Upara, Qiong Ding, Huojun Cao, Liu Hong and Ling Yang

bioRxiv

Cold Spring Harbor Laboratory

07/20/2023

DOI: 10.1101/2023.07.19.549684

PMCID: PMC10370144

PMID: 37502899

Files and links (1)

url

https://doi.org/10.1101/2023.07.19.549684View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Obesity, a worldwide health problem, increases the risk for developing metabolic diseases such as insulin resistance and diabetes. It is well recognized that obesity-associated chronic inflammation plays a key role in the pathogenesis of systemic metabolic dysfunction. Previously, we revealed an anti-inflammatory role for spent culture supernatants isolated from the oral commensal bacterial species Streptococcus gordonii (Sg-SCS). Here, we identified that 6-hydroxyhexanoic acid (6-HHA), a medium chain fatty acid (MCFA), is the one of the key components of Sg-SCS . We found that treatment of 6-HHA in mice fed a high-fat diet (HFD) significantly reduced HFD-mediated weight gain which was largely attributed to a decrease in fat mass. Systemically, 6-HHA improves obesity-associated glucose intolerance and insulin resistance. Furthermore, administration of 6-HHA suppressed obesity-associated systemic inflammation and dyslipidemia. At the cellular level, treatment of 6-HHA ameliorated aberrant inflammatory and metabolic transcriptomic signatures in white adipose tissue of mice with diet-induced obesity (HFD). Mechanistically, we found that 6-HHA suppressed adipocyte-proinflammatory cytokine production and lipolysis, the latter through Gαi-mediated signaling. This work provides direct evidence for the anti-obesity effects of a novel MCFA, which could be a new therapeutic treatment for combating obesity.

Details

Title: Subtitle: A Medium Chain Fatty Acid, 6-hydroxyhexanoic acid (6-HHA), Protects Against Obesity and Insulin Resistance
Creators: Sara C. Sebag
Qingwen Qian - University of Iowa
Chawin Upara - University of Iowa
Qiong Ding - University of Iowa
Huojun Cao
Liu Hong - University of Iowa
Ling Yang - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.1101/2023.07.19.549684
PMID: 37502899
PMCID: PMC10370144
Publisher: Cold Spring Harbor Laboratory
Language: English
Date posted: 07/20/2023
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Endodontics; Prosthodontics; Craniofacial Anomalies Research Center; Fraternal Order of Eagles Diabetes Research Center; Dental Research
Record Identifier: 9984448060302771

Metrics

41 Record Views

See more details