Energy Partitioning in Gluteal-Femoral Fat: Does the Metabolic Fate of Triglycerides Affect Coronary Heart Disease Risk?
http://www.100md.com
《动脉硬化血栓血管生物学》
From the Québec Heart Institute, Laval Hospital Research Center, Québec, Canada
Jean Vague from the University of Marseille was the first to foresee the importance of regional adipose tissue distribution when he suggested that a "male" pattern of body fat distribution, which he referred to as android obesity, was the form of obesity more likely to be accompanied by diabetes, hypertension, and heart disease, as opposed to the typical, rather benign, "female" pattern of body fatness, which he described as gynoid obesity.1 In the early 80’s, the late Per Bj?rnt?rp from the University of Gothenburg in Sweden had come across Vague’s literature, and he took advantage of the availability of anthropometric variables such as waist and hip circumferences to develop a simple index of body fat distribution, the waist to hip ratio (WHR).2–5 Having access to two prospective studies of middle-aged men and women, the Swedish team found that the proportion of abdominal fat (as crudely appreciated by the WHR) was an independent risk factor for the development of cardiovascular disease and diabetes over a follow-up period of more than a decade.2,3 Simultaneously, in the United States, Ahmed Kissebah and his group6 also generated results emphasizing the importance of regional adipose tissue distribution as an important correlate of metabolic complications that had been, in the past, associated with excess weight per se. These results published in the early 80’s have generated great interest from the scientific and medical community, and over the last 20 years a flourishing and abundant literature has been published on the topic. As for many groups around the world, the publication of Bj?rnt?rp’s early results raised our interest, and we initially focused our investigations on the study of the contribution of adipose tissue distribution to the variation of plasma lipid and lipoprotein levels. Using simple skinfold measurements as indices of subcutaneous fat accumulation, we first reported in 1985 that abdominal fat accumulation was a correlate of the reduced high-density lipoprotein (HDL)-cholesterol levels found in obesity, whereas leg fat accumulation was not associated with any evidence of metabolic prejudice whatsoever.7 With the development of imaging techniques such as MRI or computed tomography, it has been possible to measure with greater accuracy regional adipose tissue accumulation and, particularly, to distinguish subcutaneous abdominal fat from the fat located in the abdominal cavity which we described as intra-abdominal or visceral adipose tissue. In an issue of this journal published 14 years ago,8 we reviewed the evidence that we had published at that time which had clearly indicated that a selective deposition of visceral adipose tissue was associated with a whole cluster of metabolic abnormalities which were later defined as the features of the metabolic syndrome. Thus, in 1990, we had already described the relationship between abdominal fat mass, visceral adipose tissue accumulation, and the features of the atherogenic dyslipidemia of the metabolic syndrome, which include hypertriglyceridemia, elevated apolipoprotein B concentration, an increased proportion of small low-density lipoprotein (LDL) particles, and reduced HDL-cholesterol levels, particularly in the cardioprotective HDL2 subfraction.8
See page 923
In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Okura et al9 report further evidence that body fat distribution, as assessed by either dual-energy X-ray absorptiometry (DXA) or computed tomography, is an important correlate of metabolic risk variables modulating coronary heart disease risk in women. However, they found no relationship between abdominal subcutaneous adipose tissue and metabolic parameters. Not only did they find evidence that abdominal fat accumulation causes prejudice to the metabolic risk profile, but they also observed that peripheral subcutaneous fat accumulation (fat tissue in legs) might be cardioprotective. The authors also reported similar findings after a 14-week weight reduction program with diet and exercise. These results are interesting and add to the already published evidence for such cardioprotective "effect" of peripheral fat accumulation. For instance, Terry et al10 have shown that for any given waist circumference, individuals with a preferential thigh fat accumulation had a more favorable plasma lipoprotein-lipid profile. In 1991, our group also published evidence that mid-thigh fat accumulation was positively correlated with HDL2-cholesterol levels and with the HDL2-cholesterol/HDL3-cholesterol ratio, and this relationship could be explained by the elevated mid-thigh adipose tissue lipoprotein lipase activity, contributing to raise HDL2-cholesterol levels.11 Finally, also using DXA methodology, Tanko et al12 recently reported that the localization of body fat in elderly women was apparently more important than total fatness per se as a predictor of the comorbidities of obesity. They also found in that study that among women with a history of myocardial infarction, the percentage of central fat was significantly higher compared with women with no manifest coronary disease, with no differences in the percentage of peripheral fat being noted. The authors also concluded that whereas a central fat mass pattern was associated with an atherogenic profile, a peripheral fat mass pattern rather appeared to be predictive of a favorable metabolic profile.
Why Would Gluteal-Femoral Fat Be Cardioprotective?
It is possible that when exposed to an energy surplus, subcutaneous peripheral fat might represent an insulin sensitive "metabolic sink" which may, through an elevated adipose tissue lipoprotein lipase activity, favor the catabolism of triglyceride-rich lipoproteins, the clearance of triglycerides of dietary origin, and their storage in adipose cells (Figure). Such preferential partitioning of extra energy into gluteal-femoral fat in women might eventually lead to a more favorable lipid profile (lower triglyceride and increased HDL-cholesterol levels) leading to some cardioprotection. In this context, the paper by Okura and colleagues9 provides further evidence that adipose tissue is not a homogeneous organ and that it has a much more important role to play than simply the storage and mobilization of fat (Figure). In both men and women, there is probably a minimal amount of insulin-sensitive adipose tissue, which is required for the proper clearance of dietary triglycerides. A clinical example of the consequence of a lack of adipose tissue is found in the lipodystrophic patients who are characterized by a severe insulin resistant state and by ectopic triglyceride accumulation causing serious metabolic prejudice as fat accumulates in the liver, pancreas, and in muscles (Figure).13,14 Clearly, the optimal approach to limit fat accumulation in ectopic depots and in the atherogenic visceral adipose tissue is to remain in energy balance with proper nutritional habits and an adequate level of physical activity. However, a better understanding of the complex interrelationships between visceral adipose tissue accumulation and metabolic processes governing regional adipose tissue accumulation may lead to the development of new pharmacological approaches to limit ectopic fat accumulation and related health hazards. In this regard, the development of glitazones which have been shown to promote the channelling of energy in "good" subcutaneous adipose tissue has provided further evidence that regional adipose tissue distribution plays an important role, and that glitazones may create a healthy "metabolic sink" by reshaping adipose tissue distribution in previously insulin resistant individuals.15,16
Model showing the potential contribution of subcutaneous gluteal-femoral adipose tissue (AT) as a possible cardioprotective "metabolic sink". Two obesity phenotypes at both ends of the spectrum are shown: 1, The energy surplus is preferentially accumulated in gluteal-femoral fat, having little impact on the metabolic risk profile. 2, The energy surplus accumulates in the atherogenic visceral depot (which could be crudely assessed by an increased waist circumference) as well as in liver, pancreas, and muscle mass due to a lack (absolute or relative) of subcutaneous AT or in the presence of insulin resistant markedly hypertrophied adipose cells leading to a cluster of metabolic abnormalities referred to as the metabolic syndrome. CHD indicates coronary heart disease.
In summary, results of the intervention study by Okura and colleagues9 demonstrate that localization of fat mass is clearly more important than obesity per se in the evaluation of the atherogenic metabolic risk profile in women. Thus, information on regional body composition changes during weight reduction is also essential to properly evaluate the impact on coronary heart disease risk factors.
Acknowledgments
The author thanks Dr. Jean-Pierre Després for his review and feedback. Dr Lemieux is a member of a research team (Dr Després and colleagues) supported by the Canadian Institutes of Health Research.
References
Vague J. Sexual differentiation, a factor affecting the forms of obesity. Presse Méd. 1947; 30: 339–340.
Ohlson LO, Larsson B, Svardsudd K, Welin L, Eriksson H, Wilhelmsen L, Bj?rntorp P, Tibblin G. The influence of body fat distribution on the incidence of diabetes mellitus: 13.5 years of follow-up of the participants in the study of men born in 1913. Diabetes. 1985; 34: 1055–1058.
Larsson B, Svardsudd K, Welin L, Wilhelmsen L, Bj?rntorp P, Tibblin G. Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13 year follow-up of participants in the study of men born in 1913. BMJ. 1984; 288: 1401–1404.
Lapidus L, Bengtsson C, Larsson B, Pennert K, Rybo E, Sj?str?m L. Distribution of adipose tissue and risk of cardiovascular disease and death: a 12 year follow up of participants in the population study of women in Gothenburg, Sweden. BMJ. 1984; 289: 1257–1261.
Krotkiewski M, Bj?rntorp P, Sj?str?m L, Smith U. Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution. J Clin Invest. 1983; 72: 1150–1162.
Kissebah AH, Vydelingum N, Murray R, Evans DJ, Hartz AJ, Kalkhoff RK, Adams PW. Relation of body fat distribution to metabolic complications of obesity. J Clin Endocrinol Metab. 1982; 54: 254–260.
Després JP, Allard C, Tremblay A, Talbot J, Bouchard C. Evidence for a regional component of body fatness in the association with serum lipids in men and women. Metabolism. 1985; 34: 967–973.
Després JP, Moorjani S, Lupien PJ, Tremblay A, Nadeau A, Bouchard C. Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis. 1990; 10: 497–511.
Okura T, Nakata Y, Yamabuki K, Tanaka K. Regional body composition changes exhibit opposing effects on coronary heart disease risk factors. Arterioscler Thromb Vasc Biol. 2004; 24: 923–929.
Terry RB, Stefanick ML, Haskell WL, Wood PD. Contributions of regional adipose tissue depots to plasma lipoprotein concentrations in overweight men and women: possible protective effects of thigh fat. Metabolism. 1991; 40: 733–740.
Pouliot MC, Després JP, Moorjani S, Lupien PJ, Tremblay A, Nadeau A, Bouchard C. Regional variation in adipose tissue LPL activity: association with plasma high density lipoproteins levels. Eur J Clin Invest. 1991; 21: 398–405.
Tanko LB, Bagger YZ, Alexandersen P, Larsen PJ, Christiansen C. Peripheral adiposity exhibits an independent dominant antiatherogenic effect in elderly women. Circulation. 2003; 107: 1626–1631.
Schmidt HH, Genschel J, Baier P, Schmidt M, Ockenga J, Tietge UJ, Propsting M, Buttner C, Manns MP, Lochs H, Brabant G. Dyslipemia in familial partial lipodystrophy caused by an R482W mutation in the LMNA gene. J Clin Endocrinol Metab. 2001; 86: 2289–2295.
Hegele RA. Insulin resistance in human partial lipodystrophy. Curr Atheroscler Rep. 2000; 2: 397–404.
Miyazaki Y, Mahankali A, Matsuda M, Mahankali S, Hardies J, Cusi K, Mandarino LJ, DeFronzo RA. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab. 2002; 87: 2784–2791.
Mori Y, Murakawa Y, Okada K, Horikoshi H, Yokoyama J, Tajima N, Ikeda Y. Effect of troglitazone on body fat distribution in type 2 diabetic patients. Diabetes Care. 1999; 22: 908–912.(Isabelle Lemieux)
Jean Vague from the University of Marseille was the first to foresee the importance of regional adipose tissue distribution when he suggested that a "male" pattern of body fat distribution, which he referred to as android obesity, was the form of obesity more likely to be accompanied by diabetes, hypertension, and heart disease, as opposed to the typical, rather benign, "female" pattern of body fatness, which he described as gynoid obesity.1 In the early 80’s, the late Per Bj?rnt?rp from the University of Gothenburg in Sweden had come across Vague’s literature, and he took advantage of the availability of anthropometric variables such as waist and hip circumferences to develop a simple index of body fat distribution, the waist to hip ratio (WHR).2–5 Having access to two prospective studies of middle-aged men and women, the Swedish team found that the proportion of abdominal fat (as crudely appreciated by the WHR) was an independent risk factor for the development of cardiovascular disease and diabetes over a follow-up period of more than a decade.2,3 Simultaneously, in the United States, Ahmed Kissebah and his group6 also generated results emphasizing the importance of regional adipose tissue distribution as an important correlate of metabolic complications that had been, in the past, associated with excess weight per se. These results published in the early 80’s have generated great interest from the scientific and medical community, and over the last 20 years a flourishing and abundant literature has been published on the topic. As for many groups around the world, the publication of Bj?rnt?rp’s early results raised our interest, and we initially focused our investigations on the study of the contribution of adipose tissue distribution to the variation of plasma lipid and lipoprotein levels. Using simple skinfold measurements as indices of subcutaneous fat accumulation, we first reported in 1985 that abdominal fat accumulation was a correlate of the reduced high-density lipoprotein (HDL)-cholesterol levels found in obesity, whereas leg fat accumulation was not associated with any evidence of metabolic prejudice whatsoever.7 With the development of imaging techniques such as MRI or computed tomography, it has been possible to measure with greater accuracy regional adipose tissue accumulation and, particularly, to distinguish subcutaneous abdominal fat from the fat located in the abdominal cavity which we described as intra-abdominal or visceral adipose tissue. In an issue of this journal published 14 years ago,8 we reviewed the evidence that we had published at that time which had clearly indicated that a selective deposition of visceral adipose tissue was associated with a whole cluster of metabolic abnormalities which were later defined as the features of the metabolic syndrome. Thus, in 1990, we had already described the relationship between abdominal fat mass, visceral adipose tissue accumulation, and the features of the atherogenic dyslipidemia of the metabolic syndrome, which include hypertriglyceridemia, elevated apolipoprotein B concentration, an increased proportion of small low-density lipoprotein (LDL) particles, and reduced HDL-cholesterol levels, particularly in the cardioprotective HDL2 subfraction.8
See page 923
In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Okura et al9 report further evidence that body fat distribution, as assessed by either dual-energy X-ray absorptiometry (DXA) or computed tomography, is an important correlate of metabolic risk variables modulating coronary heart disease risk in women. However, they found no relationship between abdominal subcutaneous adipose tissue and metabolic parameters. Not only did they find evidence that abdominal fat accumulation causes prejudice to the metabolic risk profile, but they also observed that peripheral subcutaneous fat accumulation (fat tissue in legs) might be cardioprotective. The authors also reported similar findings after a 14-week weight reduction program with diet and exercise. These results are interesting and add to the already published evidence for such cardioprotective "effect" of peripheral fat accumulation. For instance, Terry et al10 have shown that for any given waist circumference, individuals with a preferential thigh fat accumulation had a more favorable plasma lipoprotein-lipid profile. In 1991, our group also published evidence that mid-thigh fat accumulation was positively correlated with HDL2-cholesterol levels and with the HDL2-cholesterol/HDL3-cholesterol ratio, and this relationship could be explained by the elevated mid-thigh adipose tissue lipoprotein lipase activity, contributing to raise HDL2-cholesterol levels.11 Finally, also using DXA methodology, Tanko et al12 recently reported that the localization of body fat in elderly women was apparently more important than total fatness per se as a predictor of the comorbidities of obesity. They also found in that study that among women with a history of myocardial infarction, the percentage of central fat was significantly higher compared with women with no manifest coronary disease, with no differences in the percentage of peripheral fat being noted. The authors also concluded that whereas a central fat mass pattern was associated with an atherogenic profile, a peripheral fat mass pattern rather appeared to be predictive of a favorable metabolic profile.
Why Would Gluteal-Femoral Fat Be Cardioprotective?
It is possible that when exposed to an energy surplus, subcutaneous peripheral fat might represent an insulin sensitive "metabolic sink" which may, through an elevated adipose tissue lipoprotein lipase activity, favor the catabolism of triglyceride-rich lipoproteins, the clearance of triglycerides of dietary origin, and their storage in adipose cells (Figure). Such preferential partitioning of extra energy into gluteal-femoral fat in women might eventually lead to a more favorable lipid profile (lower triglyceride and increased HDL-cholesterol levels) leading to some cardioprotection. In this context, the paper by Okura and colleagues9 provides further evidence that adipose tissue is not a homogeneous organ and that it has a much more important role to play than simply the storage and mobilization of fat (Figure). In both men and women, there is probably a minimal amount of insulin-sensitive adipose tissue, which is required for the proper clearance of dietary triglycerides. A clinical example of the consequence of a lack of adipose tissue is found in the lipodystrophic patients who are characterized by a severe insulin resistant state and by ectopic triglyceride accumulation causing serious metabolic prejudice as fat accumulates in the liver, pancreas, and in muscles (Figure).13,14 Clearly, the optimal approach to limit fat accumulation in ectopic depots and in the atherogenic visceral adipose tissue is to remain in energy balance with proper nutritional habits and an adequate level of physical activity. However, a better understanding of the complex interrelationships between visceral adipose tissue accumulation and metabolic processes governing regional adipose tissue accumulation may lead to the development of new pharmacological approaches to limit ectopic fat accumulation and related health hazards. In this regard, the development of glitazones which have been shown to promote the channelling of energy in "good" subcutaneous adipose tissue has provided further evidence that regional adipose tissue distribution plays an important role, and that glitazones may create a healthy "metabolic sink" by reshaping adipose tissue distribution in previously insulin resistant individuals.15,16
Model showing the potential contribution of subcutaneous gluteal-femoral adipose tissue (AT) as a possible cardioprotective "metabolic sink". Two obesity phenotypes at both ends of the spectrum are shown: 1, The energy surplus is preferentially accumulated in gluteal-femoral fat, having little impact on the metabolic risk profile. 2, The energy surplus accumulates in the atherogenic visceral depot (which could be crudely assessed by an increased waist circumference) as well as in liver, pancreas, and muscle mass due to a lack (absolute or relative) of subcutaneous AT or in the presence of insulin resistant markedly hypertrophied adipose cells leading to a cluster of metabolic abnormalities referred to as the metabolic syndrome. CHD indicates coronary heart disease.
In summary, results of the intervention study by Okura and colleagues9 demonstrate that localization of fat mass is clearly more important than obesity per se in the evaluation of the atherogenic metabolic risk profile in women. Thus, information on regional body composition changes during weight reduction is also essential to properly evaluate the impact on coronary heart disease risk factors.
Acknowledgments
The author thanks Dr. Jean-Pierre Després for his review and feedback. Dr Lemieux is a member of a research team (Dr Després and colleagues) supported by the Canadian Institutes of Health Research.
References
Vague J. Sexual differentiation, a factor affecting the forms of obesity. Presse Méd. 1947; 30: 339–340.
Ohlson LO, Larsson B, Svardsudd K, Welin L, Eriksson H, Wilhelmsen L, Bj?rntorp P, Tibblin G. The influence of body fat distribution on the incidence of diabetes mellitus: 13.5 years of follow-up of the participants in the study of men born in 1913. Diabetes. 1985; 34: 1055–1058.
Larsson B, Svardsudd K, Welin L, Wilhelmsen L, Bj?rntorp P, Tibblin G. Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13 year follow-up of participants in the study of men born in 1913. BMJ. 1984; 288: 1401–1404.
Lapidus L, Bengtsson C, Larsson B, Pennert K, Rybo E, Sj?str?m L. Distribution of adipose tissue and risk of cardiovascular disease and death: a 12 year follow up of participants in the population study of women in Gothenburg, Sweden. BMJ. 1984; 289: 1257–1261.
Krotkiewski M, Bj?rntorp P, Sj?str?m L, Smith U. Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution. J Clin Invest. 1983; 72: 1150–1162.
Kissebah AH, Vydelingum N, Murray R, Evans DJ, Hartz AJ, Kalkhoff RK, Adams PW. Relation of body fat distribution to metabolic complications of obesity. J Clin Endocrinol Metab. 1982; 54: 254–260.
Després JP, Allard C, Tremblay A, Talbot J, Bouchard C. Evidence for a regional component of body fatness in the association with serum lipids in men and women. Metabolism. 1985; 34: 967–973.
Després JP, Moorjani S, Lupien PJ, Tremblay A, Nadeau A, Bouchard C. Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis. 1990; 10: 497–511.
Okura T, Nakata Y, Yamabuki K, Tanaka K. Regional body composition changes exhibit opposing effects on coronary heart disease risk factors. Arterioscler Thromb Vasc Biol. 2004; 24: 923–929.
Terry RB, Stefanick ML, Haskell WL, Wood PD. Contributions of regional adipose tissue depots to plasma lipoprotein concentrations in overweight men and women: possible protective effects of thigh fat. Metabolism. 1991; 40: 733–740.
Pouliot MC, Després JP, Moorjani S, Lupien PJ, Tremblay A, Nadeau A, Bouchard C. Regional variation in adipose tissue LPL activity: association with plasma high density lipoproteins levels. Eur J Clin Invest. 1991; 21: 398–405.
Tanko LB, Bagger YZ, Alexandersen P, Larsen PJ, Christiansen C. Peripheral adiposity exhibits an independent dominant antiatherogenic effect in elderly women. Circulation. 2003; 107: 1626–1631.
Schmidt HH, Genschel J, Baier P, Schmidt M, Ockenga J, Tietge UJ, Propsting M, Buttner C, Manns MP, Lochs H, Brabant G. Dyslipemia in familial partial lipodystrophy caused by an R482W mutation in the LMNA gene. J Clin Endocrinol Metab. 2001; 86: 2289–2295.
Hegele RA. Insulin resistance in human partial lipodystrophy. Curr Atheroscler Rep. 2000; 2: 397–404.
Miyazaki Y, Mahankali A, Matsuda M, Mahankali S, Hardies J, Cusi K, Mandarino LJ, DeFronzo RA. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab. 2002; 87: 2784–2791.
Mori Y, Murakawa Y, Okada K, Horikoshi H, Yokoyama J, Tajima N, Ikeda Y. Effect of troglitazone on body fat distribution in type 2 diabetic patients. Diabetes Care. 1999; 22: 908–912.(Isabelle Lemieux)