Free fatty acids in plasma are known to be elevated in patients with type 2 diabetes and obesity, and also associated with insulin resistance and pancreatic beta (β) cell dysfunction, which results in the impaired control of blood glucose. One such fatty acid, palmitic acid (also known as hexadecanoic acid), is found in the oils of palm trees (palm oil, palm kernel oil and coconut oil) and is also present in butter, cheese, milk and meat. Research in rodents has revealed that long term exposure to palmitate (that is the salts and esters of palmitic acid) in cloned β cells or clusters of pancreatic cells (islets) alters the expression of genes involved in fatty acid metabolism and steroid biosynthesis. However, when it comes to the molecular effects of palmitate on human islets in vitro, evidence is lacking. Charlotte Ling from Lund University, Sweden, and colleagues sought to address this gap in a recent study in BMC Medicine.
Ling and colleagues show for the first time how exposure of human pancreatic islets to palmitate affects genome-wide mRNA and DNA methylation. The findings were validated by relating the gene expression levels in human islets to BMI (body-mass index) in non-diabetic individuals and to transcriptomic changes in the pancreatic islets of type 2 diabetes patients.
Pancreatic islets of eight donors were treated with palmitate for 48 hours in vitro and used in mRNA and DNA methylation array analyses, with five samples being unique for each set of microarrays. The expression levels of several specific metabolic genes as well as genes in metabolic pathways such as glycolysis, pyruvate metabolism and biosynthesis of fatty acids, were altered in palmitate treated human islets. Furthermore many differentially expressed genes showed a parallel change in DNA methylation, including candidate genes for type 2 diabetes and obesity such as TCF7L2 (Transcription Factor 7-Like 2) and GLIS3 (zinc finger transcription factor). Interestingly, some differentially expressed genes in the palmitate treated islets were found to be associated with BMI, whilst others were associated with type 2 diabetes. Moreover, bioinformatic analysis revealed that the insulin signalling pathway is enriched in both the differentially expressed and methylated genes.
The study provides original evidence that both specific and global DNA methylation patterns in human palmitate treated islets could affect mRNA expression and that lipid-induced epigenetic modifications may influence type 2 diabetes risk. The impaired insulin secretion in these cells may be of clinical relevance to obesity and type 2 diabetes. However, application to the medical field is still a long way off until targets designed for the newly identified genes show therapeutic efficacy. The study additionally has implications for the food industry where future research into palm oil derived edible products would be needed to inform health policies and help reduce the burden of obesity and type 2 diabetes.
Written by Ursula D’Souza, Senior Editor for BMC Medicine.