Protocol for a randomized placebo-controlled clinical trial using pure palmitoleic acid to ameliorate insulin resistance and lipogenesis in overweight and obese subjects with prediabetes

Front Endocrinol (Lausanne). 2024 Jan 19:14:1306528. doi: 10.3389/fendo.2023.1306528. eCollection 2023.

Abstract

Palmitoleic acid (POA), a nonessential, monounsaturated omega-7 fatty acid (C16:1n7), is a lipid hormone secreted from adipose tissue and has beneficial effects on distant organs, such as the liver and muscle. Interestingly, POA decreases lipogenesis in toxic storage sites such as the liver and muscle, and paradoxically increases lipogenesis in safe storage sites, such as adipose tissue. Furthermore, higher POA levels in humans are correlated with better insulin sensitivity, an improved lipid profile, and a lower incidence of type-2 diabetes and cardiovascular pathologies, such as myocardial infarction. In preclinical animal models, POA improves glucose intolerance, dyslipidemia, and steatosis of the muscle and liver, while improving insulin sensitivity and secretion. This double-blind placebo-controlled clinical trial tests the hypothesis that POA increases insulin sensitivity and decreases hepatic lipogenesis in overweight and obese adult subjects with pre-diabetes. Important to note, that this is the first study ever to use pure (>90%) POA with < 0.3% palmitic acid (PA), which masks the beneficial effects of POA. The possible positive findings may offer a therapeutic and/or preventative pathway against diabetes and related immunometabolic diseases.

Keywords: fatty liver; insulin resistance; obesity; overweight; palmitoleic acid; prediabetes.

Publication types

  • Clinical Trial Protocol
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Fatty Acids, Monounsaturated / therapeutic use
  • Humans
  • Insulin Resistance*
  • Lipogenesis
  • Obesity / complications
  • Obesity / drug therapy
  • Overweight / complications
  • Overweight / drug therapy
  • Prediabetic State* / complications
  • Prediabetic State* / drug therapy
  • Randomized Controlled Trials as Topic

Substances

  • Fatty Acids, Monounsaturated
  • palmitoleic acid

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This investigator-initiated study has been funded by Tersus Life Sciences, LLC with a Mass General Brigham agreement #2022A008746 and a fund #127705. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.