Visceral fat does not contribute to metabolic disease in lipodystrophy

N Malandrino, J C Reynolds, R J Brychta, K Y Chen, S Auh, A M Gharib, M Startzell, E K Cochran, R J Brown, N Malandrino, J C Reynolds, R J Brychta, K Y Chen, S Auh, A M Gharib, M Startzell, E K Cochran, R J Brown

Abstract

Objectives: Lipodystrophies are characterized by regional or generalized loss of adipose tissue and severe metabolic complications. The role of visceral adipose tissue (VAT) in the development of metabolic derangements in lipodystrophy is unknown. The study aim was to investigate VAT contribution to metabolic disease in lipodystrophy versus healthy controls.

Methods: Analysis of correlations between VAT volume and biomarkers of metabolic disease in 93 patients and 93 age/sex-matched healthy controls.

Results: Patients with generalized lipodystrophy (n = 43) had lower VAT compared with matched controls, while those with partial lipodystrophy (n = 50) had higher VAT versus controls. Both groups with lipodystrophy had lower leg fat mass versus controls (p < 0.05 for all; unpaired t-test). In both generalized and partial lipodystrophy, there was no correlation between VAT and glucose, triglycerides or high-density lipoprotein cholesterol (p > 0.05 for all; Spearman correlation). In controls matched to patients with generalized or partial lipodystrophy, VAT correlated with glucose (R = 0.42 and 0.36), triglycerides (R = 0.36 and 0.60) and high-density lipoprotein cholesterol (R = -0.34 and -0.64) (p < 0.05 for all; Spearman correlation).

Conclusions: In contrast to healthy controls, metabolic derangements in lipodystrophy did not correlate with VAT volume. These data suggest that, in lipodystrophy, impaired peripheral subcutaneous fat deposition may exert a larger effect than VAT accumulation on the development of metabolic complications. Interventions aimed at increasing functional subcutaneous adipose tissue may provide metabolic benefit.

Keywords: Lipodystrophy; subcutaneous adipose tissue; visceral adipose tissue.

Conflict of interest statement

The authors declared no conflict of interest.

Figures

Figure 1
Figure 1
Visceral adipose tissue (VAT) volume (a and b) and leg fat mass (c and d) in patients with generalized lipodystrophy (GL, red circles) and partial lipodystrophy (PL, red triangles) versus age‐matched and sex‐matched controls (blue circles and triangles). VAT volume was zero in one patient with GL, coded as 1 to permit display on a logarithmic scale. *p < 0.05.
Figure 2
Figure 2
Correlation between visceral adipose tissue (VAT) volume and biomarkers of metabolic disease in patients with generalized and partial lipodystrophy (red circles and triangles, respectively) and age‐matched and sex‐matched controls (blue circles and triangles, respectively). Log‐transformed VAT volume was significantly correlated with log‐transformed triglycerides, high‐density lipoprotein (HDL) cholesterol and fasting plasma glucose, in healthy control subjects but not in patients with generalized lipodystrophy (a–c) or partial lipodystrophy (d–f).

References

    1. Tchkonia T, Thomou T, Zhu Y, et al. Mechanisms and metabolic implications of regional differences among fat depots. Cell Metab 2013; 17: 644–656.
    1. Fox CS, Massaro JM, Hoffmann U, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation 2007; 116: 39–48.
    1. Liu J, Fox CS, Hickson DA, et al. Impact of abdominal visceral and subcutaneous adipose tissue on cardiometabolic risk factors: the Jackson Heart Study. J Clin Endocrinol Metab 2010; 95: 5419–5426.
    1. Van Pelt RE, Evans EM, Schechtman KB, Ehsani AA, Kohrt WM. Contributions of total and regional fat mass to risk for cardiovascular disease in older women. Am J Physiol Endocrinol Metab 2002; 282: E1023–E1028.
    1. Snijder MB, Visser M, Dekker JM, et al. Low subcutaneous thigh fat is a risk factor for unfavourable glucose and lipid levels, independently of high abdominal fat. The Health ABC Study. Diabetologia 2005; 48: 301–308.
    1. Zhang X, Hu EA, Wu H, Malik V, Sun Q. Associations of leg fat accumulation with adiposity‐related biological factors and risk of metabolic syndrome. Obesity (Silver Spring) 2013; 21: 824–830.
    1. Garg A. Acquired and inherited lipodystrophies. N Engl J Med 2004; 350: 1220–1234.
    1. Joseph J, Shamburek RD, Cochran EK, Gorden P, Brown RJ. Lipid regulation in lipodystrophy versus the obesity‐associated metabolic syndrome: the dissociation of HDL‐C and triglycerides. J Clin Endocrinol Metab 2014; 99: E1676–E1680.
    1. Misra A, Garg A. Clinical features and metabolic derangements in acquired generalized lipodystrophy: case reports and review of the literature. Medicine (Baltimore) 2003; 82: 129–146.
    1. Simha V, Garg A. Phenotypic heterogeneity in body fat distribution in patients with congenital generalized lipodystrophy caused by mutations in the AGPAT2 or seipin genes. J Clin Endocrinol Metab 2003; 88: 5433–5437.
    1. Akinci B, Onay H, Demir T, et al. Natural history of congenital generalized lipodystrophy: a nationwide study from Turkey. J Clin Endocrinol Metab 2016; 101: 2759–2767.
    1. Al‐Attar SA, Pollex RL, Robinson JF, et al. Quantitative and qualitative differences in subcutaneous adipose tissue stores across lipodystrophy types shown by magnetic resonance imaging. BMC Med Imaging 2007; 7: 3.
    1. Akinci B, Onay H, Demir T, et al. Clinical presentations, metabolic abnormalities and end‐organ complications in patients with familial partial lipodystrophy. Metab Clin Exp 2017; 72: 109–119.
    1. Garg A, Peshock RM, Fleckenstein JL. Adipose tissue distribution pattern in patients with familial partial lipodystrophy (Dunnigan variety). J Clin Endocrinol Metab 1999; 84: 170–174.
    1. Misra A, Peethambaram A, Garg A. Clinical features and metabolic and autoimmune derangements in acquired partial lipodystrophy: report of 35 cases and review of the literature. Medicine (Baltimore) 2004; 83: 18–34.
    1. Robertson DA, Wright R. Cirrhosis in partial lipodystrophy. Postgrad Med J 1989; 65: 318–320.
    1. Premkumar A, Chow C, Bhandarkar P, et al. Lipoatrophic‐lipodystrophic syndromes: the spectrum of findings on MR imaging. AJR Am J Roentgenol 2002; 178: 311–318.
    1. Yuh WT, Collison JS, Sickels WJ, Barloon TJ, Brennan DC, Flanigan MJ. Partial lipodystrophy. Magnetic resonance findings in one case. J Comput Tomogr 1988; 12: 287–291.
    1. Singhal PC, Sakhuja V, Jain SK, Chugh KS. Partial lipodystrophy, hypocomplementaemia and dense deposit disease. J Indian Med Assoc 1983; 81: 201–202.
    1. McNeill AD. Progressive lipodystrophy. Br J Surg 1966; 53: 216–218.
    1. Cimino JJ, Ayres EJ, Remennik L, et al. The National Institutes of Health's Biomedical Translational Research Information System (BTRIS): design, contents, functionality and experience to date. J Biomed Inform 2014; 52: 11–27.
    1. Micklesfield LK, Goedecke JH, Punyanitya M, Wilson KE, Kelly TL. Dual‐energy X‐ray performs as well as clinical computed tomography for the measurement of visceral fat. Obesity (Silver Spring) 2012; 20: 1109–1114.
    1. Kaul S, Rothney MP, Peters DM, et al. Dual‐energy X‐ray absorptiometry for quantification of visceral fat. Obesity (Silver Spring) 2012; 20: 1313–1318.
    1. Poulain‐Godefroy O, Lecoeur C, Pattou F, Fruhbeck G, Froguel P. Inflammation is associated with a decrease of lipogenic factors in omental fat in women. Am J Physiol Regul Integr Comp Physiol 2008; 295: R1–R7.
    1. Svedberg J, Stromblad G, Wirth A, Smith U, Bjorntorp P. Fatty acids in the portal vein of the rat regulate hepatic insulin clearance. J Clin Invest 1991; 88: 2054–2058.
    1. Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD. Splanchnic lipolysis in human obesity. J Clin Invest 2004; 113: 1582–1588.
    1. Vega GL, Adams‐Huet B, Peshock R, Willett D, Shah B, Grundy SM. Influence of body fat content and distribution on variation in metabolic risk. J Clin Endocrinol Metab 2006; 91: 4459–4466.
    1. Sasai H, Brychta RJ, Wood RP, et al. Does visceral fat estimated by dual‐energy X‐ray absorptiometry independently predict cardiometabolic risks in adults? J Diabetes Sci Technol 2015; 9: 917–924.
    1. Petersen KF, Oral EA, Dufour S, et al. Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J Clin Invest 2002; 109: 1345–1350.
    1. Brown RJ, Valencia A, Startzell M, et al. Metreleptin improves insulin sensitivity independent of food intake in humans with lipodystrophy. J Clin Invest 2018; 128: 3504–3516.
    1. Karpe F, Pinnick KE. Biology of upper‐body and lower‐body adipose tissue – link to whole‐body phenotypes. Nat Rev Endocrinol 2015; 11: 90–100.
    1. Manolopoulos KN, Karpe F, Frayn KN. Gluteofemoral body fat as a determinant of metabolic health. Int J Obes (Lond) 2010; 34: 949–959.
    1. Gormsen LC, Nellemann B, Sorensen LP, Jensen MD, Christiansen JS, Nielsen S. Impact of body composition on very‐low‐density lipoprotein‐triglycerides kinetics. Am J Physiol Endocrinol Metab 2009; 296: E165–E173.
    1. Nellemann B, Gormsen LC, Christiansen JS, Jensen MD, Nielsen S. Postabsorptive VLDL‐TG fatty acid storage in adipose tissue in lean and obese women. Obesity (Silver Spring) 2010; 18: 1304–1311.
    1. Votruba SB, Mattison RS, Dumesic DA, Koutsari C, Jensen MD. Meal fatty acid uptake in visceral fat in women. Diabetes 2007; 56: 2589–2597.
    1. Lotta LA, Gulati P, Day FR, et al. Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance. Nat Genet 2017; 49: 17–26.
    1. Tan GD, Savage DB, Fielding BA, et al. Fatty acid metabolism in patients with PPARgamma mutations. J Clin Endocrinol Metab 2008; 93: 4462–4470.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner