Review
Ectopic fat and cardiometabolic and vascular risk

https://doi.org/10.1016/j.ijcard.2013.08.077Get rights and content

Abstract

Given that the variation in how regional adipose tissue handles and stores excess dietary energy has substantial cardiometabolic implications, ectopic fat distribution might be an important predictor of cardiometabolic and vascular risk, in addition to overall obesity itself.

Conceptually, ectopic fat depots may be divided into systemically acting fat depots and locally acting fat depots. Systemically acting fat depots include visceral fat, fat in the liver, muscle, or neck, and subcutaneous fat. Accumulation in the abdominal visceral area, compared with overall obesity, has an equally or more important role in the development of cardiometabolic risk. Fat depots in liver/muscle tissue cause adverse cardiometabolic effects by affecting energy metabolism. Fat depots in lower-body subcutaneous areas may be protective regarding cardiometabolic risk, by trapping remnant energy. Fat accumulation in the neck is a unique type of fat depot that may increase cardiovascular risk by increasing insulin resistance.

Locally acting fat depots include pericardial fat, perivascular fat, and renal sinus fat. These fat depots have effects primarily on adjacent anatomic organs, directly via lipotoxicity and indirectly via cytokine secretion. Pericardial fat is associated with coronary atherosclerosis. Perivascular fat may play an independent role in adverse vascular biology, including arterial stiffness. Renal sinus fat is a unique fat depot that may confer additional cardiometabolic risk. Thus, ectopic fat depots may contribute to the understanding of the link between body composition and cardiometabolic risk. In this review, we focus on the role and clinical implications of ectopic fat depots in cardiometabolic and vascular risk.

Introduction

During the last decade, substantial progress has been made toward the elucidation of the pathophysiological associations between obesity and cardiometabolic diseases, including hypertension, dyslipidemia, glucose intolerance and cardiovascular disease [1].

The observation that body fat distribution, metabolic profiles, and the degree of association of these parameters with cardiovascular risk vary widely in individuals with obesity or even normal weight has been a key insight into this issue. Current data suggest that fat distribution might be a better predictor of cardiovascular disease than obesity itself [2], [3]. Body shape and how regional adipose tissue handles and stores excess dietary energy have substantial cardiometabolic implications [4], [5].

These findings have led to the hypothesis that accumulation of fat in specific locations or as ectopic fat may partially contribute to the association of adiposity with cardiometabolic risk (Fig. 1). In particular, fat accumulation in the abdominal visceral area has an important role in the development of cardiometabolic risk [6]. Fat stores in the liver and muscle are associated with insulin resistance and adverse metabolic phenotypes, independent of total adiposity [7], [8]. More recently, fat depots with primarily locally acting effects have been studied. For example, pericardial fat is associated with coronary atherosclerosis, even after accounting for abdominal fat [9]. These data support the concept that pericardial fat might have a harmful perivascular effect on the coronary arteries.

In contrast, fat depots in certain areas may be protective in terms of metabolic risk. In particular, the propensity to deposit fat in the gluteofemoral region may be associated with lower cardiometabolic risk [10]. Thus, regional fat distribution, in addition to overall fat volume, may be important in understanding the link between obesity and cardiometabolic risk. In this article, we introduce the imaging techniques used to characterize ectopic fat depots and review the literature investigating the clinical correlations and implications of ectopic fat accumulation from a cardiometabolic and vascular disease perspective. Conceptually, we consider fat depots as either those that act primarily systemically, such as abdominal visceral fat or intrahepatic fat, or those that act primarily locally, such as pericardial fat. Finally, we suggest future study directions in this area of research.

Section snippets

Imaging techniques for assessing ectopic fat depots

Various imaging techniques can be used to measure tissue composition, particularly fat, in major organs or in different compartments of the human body (Table 1 and Fig. 2).

Systemically acting ectopic fat depots

Ectopic fat depots that are particularly large (such as VAT) or that occur in organs that have central functions in metabolism (such as the liver) are considered to be primarily systemically acting fat depots [43], [44]. These fat depots are associated with systemic surrogate markers of inflammation and insulin resistance, as well as with clinical outcomes, such as type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), and stroke (Fig. 1) [1], [2], [3].

Locally acting fat depots

Locally acting fat depots are those that have effects primarily in adjacent anatomic organs. The endocrine and paracrine actions of adipocytes, especially of those neighboring cardiovascular organs, are most likely to link obesity and cardiovascular disease [117]. Locally acting fat depots may be associated with unfavorable effects on adjacent organs, directly via lipotoxicity and indirectly via the secretion of adipokines and other cytokines [118]. In particular, fat located around components

Summary

This article has described the various imaging techniques used to characterize ectopic fat depots. Representative cohort studies which assessed various adipose tissues and investigated its clinical implication are shown in Table 2. Advanced CT techniques have been used increasingly to measure ectopic fat to determine local or systemic effects on metabolic and cardiovascular risk; however, a radiation hazard is still associated with this technique. MRI is a powerful tool for assessing body

Conclusions and future directions

The deleterious effects of excess adiposity have great clinical importance. Although the reduction of whole-body fat would be ideal among individuals who have obesity, the additional benefit of targeting fat depots at specific locations in individuals at greater cardiometabolic risk represents an alternative approach.

A recent meta-analysis based on 58 cohorts has demonstrated that BMI, waist circumference, and waist-to-hip ratio (assessed singly or in combination) do not improve cardiovascular

Disclosures

The authors declare no conflict of interest.

Acknowledgment

The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. James B. Meigs is supported by 2K24 DK080140.

References (173)

  • L. Lo et al.

    Diabetes is a progression factor for hepatic fibrosis in a high fat fed mouse obesity model of non-alcoholic steatohepatitis

    J Hepatol

    (2011)
  • A. Qayyum et al.

    Evaluation of diffuse liver steatosis by ultrasound, computed tomography, and magnetic resonance imaging: which modality is best?

    Clin Imaging

    (2009)
  • L.J. Rijzewijk et al.

    Effects of hepatic triglyceride content on myocardial metabolism in type 2 diabetes

    J Am Coll Cardiol

    (2010)
  • D.I. Phillips et al.

    Intramuscular triglyceride and muscle insulin sensitivity: evidence for a relationship in nondiabetic subjects

    Metabolism

    (1996)
  • R.D. Hansen et al.

    Estimation of thigh muscle cross-sectional area by dual-energy X-ray absorptiometry in frail elderly patients

    Am J Clin Nutr

    (2007)
  • B.H. Goodpaster et al.

    Thigh adipose tissue distribution is associated with insulin resistance in obesity and in type 2 diabetes mellitus

    Am J Clin Nutr

    (2000)
  • R. Weiss et al.

    Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning

    Lancet

    (2003)
  • B. Larsson et al.

    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

    Br Med J (Clin Res Ed)

    (1984)
  • J.P. Despres et al.

    Abdominal obesity and metabolic syndrome

    Nature

    (2006)
  • C.S. Fox et al.

    Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study

    Circulation

    (2007)
  • D. Canoy et al.

    Body fat distribution and risk of coronary heart disease in men and women in the European Prospective Investigation into Cancer and Nutrition in Norfolk cohort: a population-based prospective study

    Circulation

    (2007)
  • J.P. Despres

    Is visceral obesity the cause of the metabolic syndrome?

    Ann Med

    (2006)
  • E.K. Speliotes et al.

    Fatty liver is associated with dyslipidemia and dysglycemia independent of visceral fat: the Framingham Heart Study

    Hepatology

    (2010)
  • A. Virkamaki et al.

    Intramyocellular lipid is associated with resistance to in vivo insulin actions on glucose uptake, antilipolysis, and early insulin signaling pathways in human skeletal muscle

    Diabetes

    (2001)
  • G.A. Rosito et al.

    Pericardial fat, visceral abdominal fat, cardiovascular disease risk factors, and vascular calcification in a community-based sample: the Framingham Heart Study

    Circulation

    (2008)
  • K.N. Manolopoulos et al.

    Gluteofemoral body fat as a determinant of metabolic health

    Int J Obes (Lond)

    (2010)
  • S.H. Saverymuttu et al.

    Ultrasound scanning in the detection of hepatic fibrosis and steatosis

    Br Med J (Clin Res Ed)

    (1986)
  • F.F. Ribeiro-Filho et al.

    Methods of estimation of visceral fat: advantages of ultrasonography

    Obes Res

    (2003)
  • G. Iacobellis et al.

    Epicardial fat from echocardiography: a new method for visceral adipose tissue prediction

    Obes Res

    (2003)
  • O. Lamacchia et al.

    Para- and perirenal fat thickness is an independent predictor of chronic kidney disease, increased renal resistance index and hyperuricaemia in type-2 diabetic patients

    Nephrol Dial Transplant

    (2011)
  • S. Kawasaki et al.

    Sonographic evaluation of visceral fat by measuring para- and perirenal fat

    J Clin Ultrasound

    (2008)
  • T. Yoshizumi et al.

    Abdominal fat: standardized technique for measurement at CT

    Radiology

    (1999)
  • C.S. Fox et al.

    Periaortic fat deposition is associated with peripheral arterial disease: the Framingham Heart Study

    Circ Cardiovasc Imaging

    (2010)
  • C.L. Schlett et al.

    Novel measurements of periaortic adipose tissue in comparison to anthropometric measures of obesity, and abdominal adipose tissue

    Int J Obes (Lond)

    (2009)
  • M.C. Foster et al.

    Development and reproducibility of a computed tomography-based measurement of renal sinus fat

    BMC Nephrol

    (2011)
  • J. Machann et al.

    Follow-up whole-body assessment of adipose tissue compartments during a lifestyle intervention in a large cohort at increased risk for type 2 diabetes

    Radiology

    (2010)
  • E.L. Thomas et al.

    Magnetic resonance imaging of total body fat

    J Appl Physiol

    (1998)
  • J. Machann et al.

    Standardized assessment of whole body adipose tissue topography by MRI

    J Magn Reson Imaging

    (2005)
  • H.H. Hu et al.

    Assessment of abdominal adipose tissue and organ fat content by magnetic resonance imaging

    Obes Rev

    (2011)
  • W. Shen et al.

    Pediatric obesity phenotyping by magnetic resonance methods

    Curr Opin Clin Nutr Metab Care

    (2005)
  • S.B. Reeder et al.

    Water–fat separation with IDEAL gradient-echo imaging

    J Magn Reson Imaging

    (2007)
  • A. Alabousi et al.

    Evaluation of adipose tissue volume quantification with IDEAL fat–water separation

    J Magn Reson Imaging

    (2011)
  • H. Kim et al.

    Comparative MR study of hepatic fat quantification using single-voxel proton spectroscopy, two-point dixon and three-point IDEAL

    Magn Reson Med

    (2008)
  • H.H. Hu et al.

    Comparison of fat–water MRI and single-voxel MRS in the assessment of hepatic and pancreatic fat fractions in humans

    Obesity (Silver Spring)

    (2010)
  • K. Rittig et al.

    Perivascular fatty tissue at the brachial artery is linked to insulin resistance but not to local endothelial dysfunction

    Diabetologia

    (2008)
  • J. He et al.

    Skeletal muscle lipid content and oxidative enzyme activity in relation to muscle fiber type in type 2 diabetes and obesity

    Diabetes

    (2001)
  • K.F. Petersen et al.

    Mitochondrial dysfunction in the elderly: possible role in insulin resistance

    Science

    (2003)
  • I. Lingvay et al.

    Noninvasive quantification of pancreatic fat in humans

    J Clin Endocrinol Metab

    (2009)
  • E. Sai et al.

    Association between myocardial triglyceride content and cardiac function in healthy subjects and endurance athletes

    PLoS One

    (2013)
  • K. Hind et al.

    In vivo precision of the GE Lunar iDXA densitometer for the measurement of total body composition and fat distribution in adults

    Eur J Clin Nutr

    (2011)
  • Cited by (131)

    View all citing articles on Scopus
    View full text