RNA-Seq brings new molecular insights into diabetes risk

rna-seq

Nestlé Institute of Health Sciences (NIHS) researchers have taken another step forward in understanding the variability in glycaemic improvements following weight loss in overweight and obese people, and why the risk of developing diabetes varies from one individual to the next.

Obesity is a worldwide issue and a major risk factor in the development of type 2 diabetes. A low-caloric diet (LCD) is an efficient way to lose weight and generally improve obesity-related co-morbidities, for example by improving glycaemic control. But until now, it has been unclear why some people respond differently to dieting, or why some of those who do successfully lose weight still develop type 2 diabetes

So far, LCD interventions have been performed with the assumption that most subjects would improve their glycaemic profiles. However, clinical models remained insufficient to predict the most likely outcome, and the biological factors associated with long-term outcomes were poorly understood. Research led by NIHS scientists demonstrates how, by combining omics (profiling technologies) with clinical analyses, we can better predict long-term clinical outcomes of a low-caloric diet in obese non-diabetic patients. The results of this work were published yesterday in the American Journal of Clinical Nutrition(1).

Recent NIHS research(2) investigated the link between dyslipidaemia (abnormal lipid content in the blood) and glycaemic control (maintaining normal blood glucose levels to treat or prevent diabetes), and showed a ‘fingerprint’ of lipids in blood that can be used to differentiate between pre-diabetic individuals who are likely to respond to weight loss, and those who are not (read full story).

This latest study focuses on gene expression through transcriptomics analysis, studying the changes in mRNA levels in adipose tissue during LCD and relating those changes with clinical outcomes (weight and glycaemic control) to establish whether they could induce or act as surrogate markers of differences in the way adipocytes function.

“Building on our previous research and our in-house technological expertise in characterising and quantifying the pool of relevant biological molecules, we studied the link between gene expression changes during LCD and how they relate to long-term clinical changes”, explains Armand Valsesia, an NIHS researcher in Nutrition and Metabolic Health, “with the aim of better understanding why individuals respond differently, and predict the success of dietary interventions more accurately.

“Ours is the first transcriptome-wide study involving nearly 200 subjects, making it by far the largest ever carried out in this field. It shows which genes involved in lipid metabolism are altered as a result of dietary intervention, allowing us to predict their physiological outcomes with much greater accuracy and identify those genes whose effects can be specifically modulated by diet. This represents an additional step toward the development of new and adapted nutritional solutions to help non-responders improve their metabolic health.”

Source – NIHS

Armenise C, Lefebvre G, Carayol J, Bonnel S, Bolton J, Di Cara A, Gheldof N, Descombes P, Langin D, Saris WHM, Astrup A, Hager J, Viguerie N, Valsesia A. (2017). Transcriptome profiling from adipose tissue during low-caloric diet reveals predictors of weight and glycemic outcomes in obese, non-diabetic subjects. Am J Clin Nutr 106:736–46. [article]

 

Valsesia A, Saris WHM, Astrup A, Hager J, Masoodi, M. (2016). Distinct lipid profiles predict improved glycemic control in obese, non-diabetic patients following low-caloric diet intervention: the DiOGenes randomized trial. Am J Clin Nutr 104:1–10. [article]

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