Abstract
AimWeight loss reduces risk factors associated with obesity. However, long-term metabolic improvement remains a challenge. We investigated quantitative gene expression of subcutaneous adipose tissue in obese individuals and its relationship with low calorie diet and long term weight maintenance induced changes in insulin resistance.Research DesignThree hundred eleven overweight and obese individuals followed a dietary protocol consisting of an 8-week low calorie diet followed by a 6-month ad libitum weight-maintenance diet. Individuals were clustered according to insulin resistance trajectories assessed using homeostasis model assessment of insulin resistance (HOMA-IR) index. Adipose tissue mRNA levels of 267 genes selected for regulation according to obesity, metabolic status and response to dieting was assessed using high throughput RT-qPCR. A combination of discriminant analyses was used to identify genes with regulation according to insulin resistance trajectories. Partial correlation was used to control for change in body mass index.ResultsThree different HOMA-IR profile groups were determined. HOMA-IR improved during low calorie diet in the 3 groups. At the end of the 6-month follow-up, groups A and B had reduced HOMA-IR by 50%. In group C, HOMA-IR had returned to baseline values. Genes were differentially expressed in the adipose tissue of individuals according to groups but a single gene, CIDEA, was common to all phases of the dietary intervention. Changes in adipose tissue CIDEA mRNA levels paralleled variations in insulin sensitivity independently of change in body mass index. Overall, CIDEA was up-regulated in adipose tissue of individuals with successful long term insulin resistance relapse and not in adipose tissue of unsuccessful individuals.ConclusionThe concomitant change in adipose tissue CIDEA mRNA levels and insulin sensitivity suggests a beneficial role of adipose tissue CIDEA in long term glucose homeostasis, independently of weight variation.Trial RegistrationClinicalTrials.gov NCT00390637
Highlights
Insulin resistance (IR) and type 2 diabetes are strongly associated with excess fat mass
homeostasis model assessment of insulin resistance (HOMA-IR) improved during low calorie diet in the 3 groups
Genes were differentially expressed in the adipose tissue of individuals according to groups but a single gene, CIDEA, was common to all phases of the dietary intervention
Summary
Insulin resistance (IR) and type 2 diabetes are strongly associated with excess fat mass. This is reversible with weight loss [1]. The extent to which weight loss reduces IR is heterogeneous and the improvement in IR is not stable over time [2]. The adipose tissue (AT) is a tissue devoted to energy storage as triglycerides. An overload of the buffering capacities of AT leads to a pro-inflammatory, diabetogenic and atherogenic status [3]. AT represents a key tissue in the study of obesity-related complications
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