Adipose tissue CIDEA is associated, independently of weight variation, to change in insulin resistance during a longitudinal weight control dietary program in obese individuals

Emilie Montastier, Sébastien Déjean, Caroline Le Gall, Wim H M Saris, Dominique Langin, Nathalie Viguerie, Emilie Montastier, Sébastien Déjean, Caroline Le Gall, Wim H M Saris, Dominique Langin, Nathalie Viguerie

Abstract

Aim: Weight 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 design: Three 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.

Results: Three 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.

Conclusion: The 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 registration: ClinicalTrials.gov NCT00390637.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Flowchart for individuals' selection from…
Figure 1. Flowchart for individuals' selection from the DiOGenes cohort.
Participants entering subsequent phases of the study as well as dropouts are indicated in total. AT, adipose tissue; CID, clinical investigation day; HGI, high glycemic index; HOMA-IR, Individual Homeostasis Model Assessment of Insulin Resistance; HP, high protein; LCD, low calorie diet; LGI, low glycemic index; LP, low protein; WMD, weight maintenance diet.
Figure 2. Clustering of insulin resistance profiles…
Figure 2. Clustering of insulin resistance profiles in obese individuals during the dietary intervention (n = 216).
Individual Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) changes during an 8-week calorie restriction (LCD) and a 6-month weight maintenance diet (WMD) were clustered, resulting in 3 groups. The panel shows mean HOMA-IR changes expressed as change after LCD and at the end of the 6-montho weight maintenance (WMD) vs. baseline (BAS) values according to groups. The black line shows the HOMA-IR profile for group A (n = 94). The dashed line shows the HOMA-IR profile for group B (n = 48). The dotted line shows the HOMA-IR profile for group C (n = 74). The A, B, and C are the mean of HOMA-IR changes in each clustered group. ◊: p<0.05, data different in group A. Δ: p<0.05, data different in group B. #: p<0.05, data different in group C. §: p<0.05, data difference between groups. Values are means ± SEM.
Figure 3. Human adipose tissue CIDEA gene…
Figure 3. Human adipose tissue CIDEA gene expression according to insulin resistance profiles (n = 216).
Relative CIDEA mRNA levels in subcutaneous adipose tissue were plotted according to groups compared to baseline, after 8 weeks low calorie diet (LCD, white bars), and after 6 months of weight maintenance diet (WMD, black bars). AT, adipose tissue; HOMA-IR, Homeostasis Model Assessment of Insulin Resistance. *: p<0.05, difference between baseline and the end of LCD or WMD. Values are means ± SEM.
Figure 4. Adipose tissue CIDEA gene expression…
Figure 4. Adipose tissue CIDEA gene expression according to improvement of insulin sensitivity during dietary intervention (n = 311).
CIDEA mRNA levels fold change (FC) in subcutaneous adipose tissue were plotted according to FC in HOMA-IR during the entire dietary intervention. AT, adipose tissue; HOMA-IR, Homeostasis Model Assessment of Insulin Resistance. *: p

References

    1. Wing RR, Lang W, Wadden TA, Safford M, Knowler WC, et al. (2011) Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes care 34: 1481–1486.
    1. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, et al. (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. The New England journal of medicine 344: 1343–1350.
    1. Sun K, Kusminski CM, Scherer PE (2011) Adipose tissue remodeling and obesity. The Journal of clinical investigation 121: 2094–2101.
    1. Lappalainen T, Sammeth M, Friedlander MR, Hoen PA, Monlong J, et al. (2013) Transcriptome and genome sequencing uncovers functional variation in humans. Nature 501: 506–511.
    1. Keller MP, Attie AD (2010) Physiological insights gained from gene expression analysis in obesity and diabetes. Annual review of nutrition 30: 341–364.
    1. Larsen TM, Dalskov SM, van Baak M, Jebb SA, Papadaki A, et al. (2010) Diets with high or low protein content and glycemic index for weight-loss maintenance. The New England journal of medicine 363: 2102–2113.
    1. Baecke JA, Burema J, Frijters JE (1982) A short questionnaire for the measurement of habitual physical activity in epidemiological studies. The American journal of clinical nutrition 36: 936–942.
    1. Larsen TM, Dalskov S, van Baak M, Jebb S, Kafatos A, et al. (2010) The Diet, Obesity and Genes (Diogenes) Dietary Study in eight European countries - a comprehensive design for long-term intervention. Obesity reviews : an official journal of the International Association for the Study of Obesity 11: 76–91.
    1. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, et al. (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28: 412–419.
    1. Viguerie N, Montastier E, Maoret JJ, Roussel B, Combes M, et al. (2012) Determinants of human adipose tissue gene expression: impact of diet, sex, metabolic status, and cis genetic regulation. PLoS genetics 8: e1002959.
    1. Klimcakova E, Roussel B, Kovacova Z, Kovacikova M, Siklova-Vitkova M, et al. (2011) Macrophage gene expression is related to obesity and the metabolic syndrome in human subcutaneous fat as well as in visceral fat. Diabetologia 54: 876–887.
    1. Marquez-Quinones A, Mutch DM, Debard C, Wang P, Combes M, et al. (2010) Adipose tissue transcriptome reflects variations between subjects with continued weight loss and subjects regaining weight 6 mo after caloric restriction independent of energy intake. The American journal of clinical nutrition 92: 975–984.
    1. Capel F, Klimcakova E, Viguerie N, Roussel B, Vitkova M, et al. (2009) Macrophages and adipocytes in human obesity: adipose tissue gene expression and insulin sensitivity during calorie restriction and weight stabilization. Diabetes 58: 1558–1567.
    1. Capel F, Viguerie N, Vega N, Dejean S, Arner P, et al. (2008) Contribution of energy restriction and macronutrient composition to changes in adipose tissue gene expression during dietary weight-loss programs in obese women. The Journal of clinical endocrinology and metabolism 93: 4315–4322.
    1. de la Fuente A, Bing N, Hoeschele I, Mendes P (2004) Discovery of meaningful associations in genomic data using partial correlation coefficients. Bioinformatics 20: 3565–3574.
    1. Puri V, Ranjit S, Konda S, Nicoloro SM, Straubhaar J, et al. (2008) Cidea is associated with lipid droplets and insulin sensitivity in humans. Proceedings of the National Academy of Sciences of the United States of America 105: 7833–7838.
    1. Abdul-Ghani MA, Jenkinson CP, Richardson DK, Tripathy D, DeFronzo RA (2006) Insulin secretion and action in subjects with impaired fasting glucose and impaired glucose tolerance: results from the Veterans Administration Genetic Epidemiology Study. Diabetes 55: 1430–1435.
    1. Antuna-Puente B, Disse E, Rabasa-Lhoret R, Laville M, Capeau J, et al. (2011) How can we measure insulin sensitivity/resistance? Diabetes & metabolism 37: 179–188.
    1. Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, et al. (2000) Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes care 23: 57–63.
    1. Chalmers J, MacMahon S, Mancia G, Whitworth J, Beilin L (1999) 1999 World Health Organization-International Society of Hypertension Guidelines for the Management of Hypertension. Guidelines Subcommittee. Journal of hypertension 17: 151–183.
    1. Lin SC, Li P (2004) CIDE-A, a novel link between brown adipose tissue and obesity. Trends in molecular medicine 10: 434–439.
    1. Gong J, Sun Z, Li P (2009) CIDE proteins and metabolic disorders. Current opinion in lipidology 20: 121–126.
    1. Yonezawa T, Kurata R, Kimura M, Inoko H (2011) Which CIDE are you on? Apoptosis and energy metabolism. Molecular bioSystems 7: 91–100.
    1. Nordstrom EA, Ryden M, Backlund EC, Dahlman I, Kaaman M, et al. (2005) A human-specific role of cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) in adipocyte lipolysis and obesity. Diabetes 54: 1726–1734.
    1. Dahlman I, Linder K, Arvidsson Nordstrom E, Andersson I, Liden J, et al. (2005) Changes in adipose tissue gene expression with energy-restricted diets in obese women. The American journal of clinical nutrition 81: 1275–1285.
    1. Johansson LE, Danielsson AP, Parikh H, Klintenberg M, Norstrom F, et al. (2012) Differential gene expression in adipose tissue from obese human subjects during weight loss and weight maintenance. The American journal of clinical nutrition 96: 196–207.
    1. Alligier M, Gabert L, Meugnier E, Lambert-Porcheron S, Chanseaume E, et al. (2013) Visceral fat accumulation during lipid overfeeding is related to subcutaneous adipose tissue characteristics in healthy men. The Journal of clinical endocrinology and metabolism 98: 802–810.
    1. Mutch DM, Pers TH, Temanni MR, Pelloux V, Marquez-Quinones A, et al. (2011) A distinct adipose tissue gene expression response to caloric restriction predicts 6-mo weight maintenance in obese subjects. The American journal of clinical nutrition 94: 1399–1409.
    1. Gummesson A, Jernas M, Svensson PA, Larsson I, Glad CA, et al. (2007) Relations of adipose tissue CIDEA gene expression to basal metabolic rate, energy restriction, and obesity: population-based and dietary intervention studies. The Journal of clinical endocrinology and metabolism 92: 4759–4765.
    1. Laurencikiene J, Stenson BM, Arvidsson Nordstrom E, Agustsson T, Langin D, et al. (2008) Evidence for an important role of CIDEA in human cancer cachexia. Cancer research 68: 9247–9254.
    1. Brasaemle DL (2007) Thematic review series: adipocyte biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis. Journal of lipid research 48: 2547–2559.
    1. Greenberg AS, Coleman RA, Kraemer FB, McManaman JL, Obin MS, et al. (2011) The role of lipid droplets in metabolic disease in rodents and humans. The Journal of clinical investigation 121: 2102–2110.
    1. Zhou Z, Yon Toh S, Chen Z, Guo K, Ng CP, et al. (2003) Cidea-deficient mice have lean phenotype and are resistant to obesity. Nature genetics 35: 49–56.
    1. Christianson JL, Boutet E, Puri V, Chawla A, Czech MP (2010) Identification of the lipid droplet targeting domain of the Cidea protein. Journal of lipid research 51: 3455–3462.
    1. Girousse A, Tavernier G, Valle C, Moro C, Mejhert N, et al. (2013) Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass. PLoS biology 11: e1001485.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner