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

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.

Rapid Movement of Palmitoleic Acid from Phosphatidylcholine to Phosphatidylinositol in Activated Human Monocytes

“…Recent research has brought another monounsaturated fatty acid, palmitoleic acid ( cis -9-hexadecenoic acid, 16:1n–7, POA), into the limelight of inflammatory lipid research due to its protective effects against hepatic steatosis and its role in enhancing insulin signaling in murine models of metabolic disorders [ 16 , 17 ]. Elevated levels of POA in humans have been shown to correlate with improved insulin sensitivity, a favorable lipid profile, and the reduced incidence of type-2 diabetes and cardiovascular diseases such as myocardial infarction [ 18 ]. Additionally, POA reduces inflammation by decreasing circulating pro-inflammatory cytokines and inflammatory markers in various tissues [ 19 , 20 , 21 , 22 , 23 , 24 ].…”