Gene Expression in Obesity and Insulin Resistance
Condition: Insulin Resistance; Metabolic Syndrome
MeSH terms: Metabolic Syndrome; Insulin Resistance
Study type: Interventional

Summary: 
      Lifestyle and genetic factors interact in the development of obesity and the metabolic
      syndrome. The molecular mechanisms underlying the beneficial dietary modifications are,
      however, unclear. We aimed to examine the effect of the long-term 30 moderate weight
      reduction on gene expression in adipose tissue (AT) and to identify genes and gene clusters
      responsive to treatment and thereby likely contributing to the development of the metabolic
      syndrome. Thus, randomized controlled and individualized weight reduction and physical
      exercise intervention was conducted. In the WR group, glucose metabolism improved that was
      not seen in other groups. Moreover, an inverse correlation between the change in SI and the
      change in body weight was found (r =-0.44, p=0.026). Down-regulation of gene expression
      (p<0.01) involving gene ontology groups of extracellular matrix, cell death was seen. Such
      changes did not occur in the other groups.
    

Detailed description: 
      The objective of the study is to examine the expression of genes and gene regions involved in
      obesity, insulin resistance and lipid metabolism. We aim to identify new genes which are
      involved in the development of metabolic aberrations characteristic of metabolic
      syndrome/type 2 diabetes. Obesity and type 2 diabetes are increasing medical and public
      health problems globally. Low HDL cholesterol and elevated triglyceride concentrations, and
      altered cholesterol metabolism are common in these states. More knowledge is urgently needed
      of the role of genetics in obesity, insulin resistance and abnormal lipid metabolism and
      their mutual relationship. This would enable the early detection of subjects at increased
      risk of developing obesity and the common abnormalities related to it, i.e. insulin
      resistance and abnormal lipid metabolism, as well as identification of subjects with
      genotypes associated with increased risk for above mentioned metabolic states and
      atherosclerotic vascular diseases and decreased responsiveness to conventional treatment.
      Because both weight loss and regular physical exercise result in substantial changes in
      glucose, insulin and lipid metabolism, studies aiming to explore the function of relevant
      genes are highly interesting. In this study, gene expression will be measured in adipose
      tissue and leucocytes before and after weight loss or period of regular physical exercise.

      Originally, the Genobin study included 75 middle-aged (mean age 60±7 years) overweight or
      obese (mean BMI 32.9±2.8 kg/m2) men and women with impaired fasting glucose (fasting plasma
      glucose concentration 5.6-7.0 mmol/l) or impaired glucose tolerance (2-hour plasma glucose
      concentration 7.8-11.0 mmol/l and fasting plasma glucose <7.1 mmol/l) and two additional
      features of metabolic syndrome according to the Adult Treatment Panel III criteria [49] (for
      details see [50]). Subjects were randomized to one of the following groups: weight reduction
      (WR) (n=28), aerobic exercise training (n=15), resistance exercise training (n=14) or control
      group (n=18). Subjects were matched for age, sex and the status of glucose metabolism. In
      addition, 11 normal-weight subjects (mean age 48±9 years, mean BMI 23.7±1.9 kg/m2) were
      recruited. The intervention was performed in accordance with the standards of the Helsinki
      Declaration. The Ethics Committee of the District Hospital Region of Northern Savo and Kuopio
      University Hospital approved the study plan, and all participants gave written informed
      consent.

      At the beginning of the study and after 9-11 months the following measurements were
      performed: plasma/serum concentrations of glucose, insulin, total and lipoprotein lipids,
      free fatty acids, non-cholesterol sterols, glycerol, leptin, adiponectin, ghrelin, tumor
      necrosis factor α, and C-reactive protein, waist and hip circumferences, body composition and
      resting energy expenditure. A DNA sample were drawn and an adipose tissue biopsy was
      performed. A frequently sampled intravenous glucose tolerance test (FSIGT) was performed to
      assess insulin sensitivity and secretion. Given biochemical measurements were performed also
      at 3 months.
    

Intervention name(s): Weight reduction, Resistance training, Aerobic exercise training, Control
Intervention type(s): Behavioral
Intervention description(s): Weight reduction: 12 weeks intensive weight loss, 20 weeks maintenance Resistance and aerobic exercise training: individualized and progressive training programs
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Insulin resistance, weight reduction, adipose tissue, peripheral; mononuclear cells, gene expression profile, transcriptomics