Skip to main content
Top
Published in: Diabetologia 11/2005

01-11-2005 | Article

Prospective and controlled studies of the actions of insulin and catecholamine in fat cells of obese women following weight reduction

Authors: P. Löfgren, J. Hoffstedt, E. Näslund, M. Wirén, P. Arner

Published in: Diabetologia | Issue 11/2005

Login to get access

Abstract

Aims/hypothesis

Enlarged fat cells from obese subjects are characterised by insulin resistance and abnormal adrenergic regulation of lipolysis. The aim of the present study was to examine whether these aberrations return to normal following weight reduction.

Materials and methods

Obese women (n=25) were investigated before and 3±1 years (mean±SD) after steady-state weight reduction and compared with control women who were matched to the cases at re-examination in terms of age and BMI. Adipocyte volume, lipogenesis and lipolysis were determined in isolated subcutaneous fat cells following stimulation or inhibition at different steps of the lipolytic cascade.

Results

Weight reduction decreased fat cell volume and basal and adrenergic-regulated lipolysis rates to values that were 20–40% lower than those in control women (p=0.0002–0.03), despite the fact that percentage body fat was almost identical in the two groups of women. Fat cell volume was directly proportional to lipolysis in obese subjects, both before and after weight reduction, and in control subjects. Insulin-induced antilipolysis and lipogenesis were completely normalised after weight reduction.

Conclusions/interpretation

Body-weight-reduced obese women had low basal and catecholamine-stimulated adipocyte lipolysis, presumably due to adipose tissue hyperplasia. This could make an important contribution to body weight gain following weight loss. Adipocyte insulin resistance is secondary to obesity.
Literature
1.
go back to reference Prins JB, O’Rahilly S (1997) Regulation of adipose cell number in man. Clin Sci (Lond) 92:3–11 Prins JB, O’Rahilly S (1997) Regulation of adipose cell number in man. Clin Sci (Lond) 92:3–11
2.
go back to reference Large V, Arner P (1998) Regulation of lipolysis in humans. Pathophysiological modulation in obesity, diabetes and hyperlipidaemia. Diabetes Metab 24:409–418PubMed Large V, Arner P (1998) Regulation of lipolysis in humans. Pathophysiological modulation in obesity, diabetes and hyperlipidaemia. Diabetes Metab 24:409–418PubMed
3.
go back to reference Arner P (1998) Control of lipolysis and its relevance to development of obesity in man. Diabetes Metab Rev 4:409–418 Arner P (1998) Control of lipolysis and its relevance to development of obesity in man. Diabetes Metab Rev 4:409–418
4.
go back to reference Caro JF, Dohm LG, Pories WJ, Sinah MK (1989) Cellular alterations in liver, skeletal muscle, and adipose tissue responsible for insulin resistance in obesity and type II diabetes. Diabetes Metab Rev 5:665–689PubMed Caro JF, Dohm LG, Pories WJ, Sinah MK (1989) Cellular alterations in liver, skeletal muscle, and adipose tissue responsible for insulin resistance in obesity and type II diabetes. Diabetes Metab Rev 5:665–689PubMed
6.
go back to reference LaFontan M, Berlan M (1995) Fat cell alpha 2-adrenoceptors: the regulation of fat cell function and lipolysis. Endocr Rev 16:716–738CrossRefPubMed LaFontan M, Berlan M (1995) Fat cell alpha 2-adrenoceptors: the regulation of fat cell function and lipolysis. Endocr Rev 16:716–738CrossRefPubMed
7.
go back to reference Coppack SW, Jensen MD, Miles JM (1994) In vivo regulation of lipolysis in humans. J Lipid Res 35:177–193PubMed Coppack SW, Jensen MD, Miles JM (1994) In vivo regulation of lipolysis in humans. J Lipid Res 35:177–193PubMed
8.
go back to reference Mauriege P, Despres JP, Prud’homme D et al (1991) Regional variation in adipose tissue lipolysis in lean and obese men. J Lipid Res 32:1625–1633PubMed Mauriege P, Despres JP, Prud’homme D et al (1991) Regional variation in adipose tissue lipolysis in lean and obese men. J Lipid Res 32:1625–1633PubMed
9.
go back to reference Reynisdottir S, Wahrenberg H, Carlstrom K, Rossner S, Arner P (1994) Catecholamine resistance in fat cells of women with upper body obesity due to decreased expression of beta 2-adrenoceptors. Diabetologia 37:428–435PubMed Reynisdottir S, Wahrenberg H, Carlstrom K, Rossner S, Arner P (1994) Catecholamine resistance in fat cells of women with upper body obesity due to decreased expression of beta 2-adrenoceptors. Diabetologia 37:428–435PubMed
10.
go back to reference Large V, Reynisdottir S, Langin D et al (1999) Decreased expression and function of adipocyte hormone-sensitive lipase in subcutaneous fat cells of obese subjects. J Lipid Res 40:2059–2066PubMed Large V, Reynisdottir S, Langin D et al (1999) Decreased expression and function of adipocyte hormone-sensitive lipase in subcutaneous fat cells of obese subjects. J Lipid Res 40:2059–2066PubMed
11.
go back to reference Holm C (2003) Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Biochem Soc Trans 31:1120–1124PubMed Holm C (2003) Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Biochem Soc Trans 31:1120–1124PubMed
12.
go back to reference Nicklas BJ, Rogus EM, Berman DM, Dennis KE, Goldberg AP (2000) Responses of adipose tissue lipoprotein lipase to weight loss affect lipid levels and weight regain in women. Am J Physiol Endocrinol Metab 279:E1012–E1019PubMed Nicklas BJ, Rogus EM, Berman DM, Dennis KE, Goldberg AP (2000) Responses of adipose tissue lipoprotein lipase to weight loss affect lipid levels and weight regain in women. Am J Physiol Endocrinol Metab 279:E1012–E1019PubMed
13.
go back to reference Dennis KE, Goldberg AP (1993) Differential effects of body fatness and body fat distribution on risk factor for cardiovascular disease in women. Impact of weight loss. Arterioscler Thromb 13:1487–1494PubMed Dennis KE, Goldberg AP (1993) Differential effects of body fatness and body fat distribution on risk factor for cardiovascular disease in women. Impact of weight loss. Arterioscler Thromb 13:1487–1494PubMed
14.
go back to reference Goodpaster BH, Kelley DE, Wing RR, Meier A, Thaete FL (1999) Effects of weight loss on regional fat distribution and insulin sensitivity in obesity. Diabetes 48:839–847PubMed Goodpaster BH, Kelley DE, Wing RR, Meier A, Thaete FL (1999) Effects of weight loss on regional fat distribution and insulin sensitivity in obesity. Diabetes 48:839–847PubMed
15.
go back to reference Löfgren P, Hoffstedt J, Rydén M et al (2002) Major gender differences in the lipolytic capacity of abdominal subcutaneous fat cells in obesity observed before and after long-term weight reduction. J Clin Endocrinol Metab 87:764–771CrossRefPubMed Löfgren P, Hoffstedt J, Rydén M et al (2002) Major gender differences in the lipolytic capacity of abdominal subcutaneous fat cells in obesity observed before and after long-term weight reduction. J Clin Endocrinol Metab 87:764–771CrossRefPubMed
16.
go back to reference Hellström L, Reynisdottir S (2000) Influence of heredity for obesity on adipocyte lipolysis in lean and obese subjects. Int J Obes Relat Metab Disord 24:340–344CrossRefPubMed Hellström L, Reynisdottir S (2000) Influence of heredity for obesity on adipocyte lipolysis in lean and obese subjects. Int J Obes Relat Metab Disord 24:340–344CrossRefPubMed
17.
go back to reference Hellström L, Langin D, Reynisdottir S, Dauzats M, Arner P (1996) Adipocyte lipolysis in normal weight subjects with obesity among first-degree relatives. Diabetologia 39:921–928PubMed Hellström L, Langin D, Reynisdottir S, Dauzats M, Arner P (1996) Adipocyte lipolysis in normal weight subjects with obesity among first-degree relatives. Diabetologia 39:921–928PubMed
18.
go back to reference Kolaczynski JW, Morales LM, Moore JH Jr et al (1994) A new technique for biopsy of human abdominal fat under local anaesthesia with Lidocaine. Int J Obes Relat Metab Disord 18:161–166PubMed Kolaczynski JW, Morales LM, Moore JH Jr et al (1994) A new technique for biopsy of human abdominal fat under local anaesthesia with Lidocaine. Int J Obes Relat Metab Disord 18:161–166PubMed
19.
go back to reference Rodbell M (1964) Metabolism of isolated fat cells. Effects of hormones on glucose metabolism and lipolysis. J Biol Chem 239:375–380PubMed Rodbell M (1964) Metabolism of isolated fat cells. Effects of hormones on glucose metabolism and lipolysis. J Biol Chem 239:375–380PubMed
20.
go back to reference Hirsch J, Gallian E (1968) Methods for determination of adipose cell size and cell number in man and animals. J Lipid Res 9:110–119PubMed Hirsch J, Gallian E (1968) Methods for determination of adipose cell size and cell number in man and animals. J Lipid Res 9:110–119PubMed
21.
go back to reference Hellmér J, Arner P, Lundin A (1989) Automatic luminometric kinetic assay of glycerol for lipolysis studies. Anal Biochem 177:132–137CrossRefPubMed Hellmér J, Arner P, Lundin A (1989) Automatic luminometric kinetic assay of glycerol for lipolysis studies. Anal Biochem 177:132–137CrossRefPubMed
22.
go back to reference Lönnqvist F, Wennlund A, Arner P (1988) Antilipolytic effects of insulin and adenylate cyclase inhibitors on isolated human fat cells. Int J Obes 13:137–146 Lönnqvist F, Wennlund A, Arner P (1988) Antilipolytic effects of insulin and adenylate cyclase inhibitors on isolated human fat cells. Int J Obes 13:137–146
23.
go back to reference Östman J, Arner P, Kimura H, Wahrenberg H, Engfeldt P (1984) Influence of fasting on lipolytic response to adrenergic agonists and adrenergic receptors in subcutaneous adipocytes. Eur J Clin Invest 14:383–391PubMed Östman J, Arner P, Kimura H, Wahrenberg H, Engfeldt P (1984) Influence of fasting on lipolytic response to adrenergic agonists and adrenergic receptors in subcutaneous adipocytes. Eur J Clin Invest 14:383–391PubMed
24.
go back to reference Arner P, Engfeldt P (1987) Fasting mediated alteration studies of insulin action on lipolysis and lipogenesis in obese women. Am J Physiol 253:193–201 Arner P, Engfeldt P (1987) Fasting mediated alteration studies of insulin action on lipolysis and lipogenesis in obese women. Am J Physiol 253:193–201
25.
go back to reference Chen MK (1981) Paired t-test, negative intraclass correlations, and case-control studies. Am J Clin Nutr 34:956–959 Chen MK (1981) Paired t-test, negative intraclass correlations, and case-control studies. Am J Clin Nutr 34:956–959
26.
go back to reference Mauriege P, Imbeault P, Langin D et al (1999) Regional and gender variations in adipose tissue lipolysis in response to weight loss. J Lipid Res 40:1559–1571PubMed Mauriege P, Imbeault P, Langin D et al (1999) Regional and gender variations in adipose tissue lipolysis in response to weight loss. J Lipid Res 40:1559–1571PubMed
27.
go back to reference Smith U (1970) Insulin responsiveness and lipid synthesis in human fat cells of different sizes: effect of the incubation medium. Biochim Biophys Acta 218:417–423PubMed Smith U (1970) Insulin responsiveness and lipid synthesis in human fat cells of different sizes: effect of the incubation medium. Biochim Biophys Acta 218:417–423PubMed
28.
go back to reference Weyer C, Foley JE, Bogardus C, Tatarinni PA, Pratley RE (2000) Enlarged subcutaneous abdominal adipocyte size, but not obesity it self, predicts type 2 diabetes independent of insulin resistance. Diabetologia 43:1498–1506CrossRefPubMed Weyer C, Foley JE, Bogardus C, Tatarinni PA, Pratley RE (2000) Enlarged subcutaneous abdominal adipocyte size, but not obesity it self, predicts type 2 diabetes independent of insulin resistance. Diabetologia 43:1498–1506CrossRefPubMed
29.
go back to reference Hellström L, Reynisdottir S, Langin D, Rössner S, Arner P (1996) Regulation of lipolysis in fat cells of obese women during long-term hypocaloric diet. Int J Metab Disord 20:745–752 Hellström L, Reynisdottir S, Langin D, Rössner S, Arner P (1996) Regulation of lipolysis in fat cells of obese women during long-term hypocaloric diet. Int J Metab Disord 20:745–752
30.
go back to reference Rozen R, Banegas E, Davilla M, Apfelbaum M (1984) Effects of a very-low-calorie diet on adrenergic responsiveness in human adipose tissue. Int J Obes 8:141–149PubMed Rozen R, Banegas E, Davilla M, Apfelbaum M (1984) Effects of a very-low-calorie diet on adrenergic responsiveness in human adipose tissue. Int J Obes 8:141–149PubMed
31.
go back to reference Crampes F, Marceron M, Beauville M et al (1989) Platelet alpha2-adrenoceptors and adrenergic adipose tissue responsiveness after moderate hypocaloric diet in obese subjects. Int J Obes 13:99–110PubMed Crampes F, Marceron M, Beauville M et al (1989) Platelet alpha2-adrenoceptors and adrenergic adipose tissue responsiveness after moderate hypocaloric diet in obese subjects. Int J Obes 13:99–110PubMed
32.
go back to reference Presta E, Leibel RL, Hirsch J (1990) Regional changes in adrenergic receptor status during hypocaloric intake do not predict changes in adipocyte size or body shape. Metabolism 39:307–315CrossRefPubMed Presta E, Leibel RL, Hirsch J (1990) Regional changes in adrenergic receptor status during hypocaloric intake do not predict changes in adipocyte size or body shape. Metabolism 39:307–315CrossRefPubMed
33.
go back to reference Stich V, Harant I, De Glisezinski I (1997) Adipose tissue lipolysis and hormone-sensitive lipase expression during very-low-calorie diet in female identical twins. J Clin Endocrinol Metab 82:739–744CrossRefPubMed Stich V, Harant I, De Glisezinski I (1997) Adipose tissue lipolysis and hormone-sensitive lipase expression during very-low-calorie diet in female identical twins. J Clin Endocrinol Metab 82:739–744CrossRefPubMed
34.
go back to reference Kather H, Wieland E, Fischer B, Wirth A, Schlierf G (1985) Adrenergic regulation of lipolysis in abdominal adipocytes of obese subjects during caloric restriction: reversal of catecholamine action caused by relief of endogenous inhibition. Eur J Clin Invest 15:30–37PubMed Kather H, Wieland E, Fischer B, Wirth A, Schlierf G (1985) Adrenergic regulation of lipolysis in abdominal adipocytes of obese subjects during caloric restriction: reversal of catecholamine action caused by relief of endogenous inhibition. Eur J Clin Invest 15:30–37PubMed
35.
go back to reference Berlan M, Dang-Tran L, Lafontan M, Denard Y (1981) Influence of hypocaloric diet on alpha-adrenergic responsiveness of obese human subcutaneous adipocytes. Int J Obes 5:145–153PubMed Berlan M, Dang-Tran L, Lafontan M, Denard Y (1981) Influence of hypocaloric diet on alpha-adrenergic responsiveness of obese human subcutaneous adipocytes. Int J Obes 5:145–153PubMed
36.
go back to reference Smith U, Hammersten J, Björntorp P, Kral JG (1979) Regional differences and effect of weight reduction on human fat cell metabolism. Eur J Clin Invest 9:327–332PubMed Smith U, Hammersten J, Björntorp P, Kral JG (1979) Regional differences and effect of weight reduction on human fat cell metabolism. Eur J Clin Invest 9:327–332PubMed
37.
go back to reference Reynisdottir S, Langin D, Carlstrom K, Holm C, Rossner S, Arner P (1995) Effects of weight reduction on the regulation of lipolysis and adipocytes of women with upper-body obesity. Clin Sci (Lond) 89:421–429 Reynisdottir S, Langin D, Carlstrom K, Holm C, Rossner S, Arner P (1995) Effects of weight reduction on the regulation of lipolysis and adipocytes of women with upper-body obesity. Clin Sci (Lond) 89:421–429
38.
go back to reference Large V, Arner P, Reynisdottir S et al (1998) Hormone sensitive lipase expression and activity in relation to lipolysis in human fat cells. J Lipid Res 39:1688–1695PubMed Large V, Arner P, Reynisdottir S et al (1998) Hormone sensitive lipase expression and activity in relation to lipolysis in human fat cells. J Lipid Res 39:1688–1695PubMed
39.
go back to reference Vazquez LA, Pazos F, Berrazueta JR et al (2005) Effects of changes in body weight and insulin resistance on inflammation and endothelial function in morbid obesity after bariatric surgery. J Clin Endocrinol Metab 90:316–322CrossRefPubMed Vazquez LA, Pazos F, Berrazueta JR et al (2005) Effects of changes in body weight and insulin resistance on inflammation and endothelial function in morbid obesity after bariatric surgery. J Clin Endocrinol Metab 90:316–322CrossRefPubMed
Metadata
Title
Prospective and controlled studies of the actions of insulin and catecholamine in fat cells of obese women following weight reduction
Authors
P. Löfgren
J. Hoffstedt
E. Näslund
M. Wirén
P. Arner
Publication date
01-11-2005
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 11/2005
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-005-1961-6

Other articles of this Issue 11/2005

Diabetologia 11/2005 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.