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Introduction: Lipodystrophy is a rare disease characterized by the loss of adipose tissue. Visceral adipose tissue loss in certain forms of lipodystrophy may affect the amount of mesenteric fat., Method: We studied visceral adipose tissue by measuring the thickness of mesenteric and retroperitoneal adipose tissue and the aortomesenteric (AOM) distance in patients with genetic forms of lipodystrophy (n = 48; 7 males; 41 females; mean age 39.1 ± 11.9 years; 19 with congenital generalized lipodystrophy [CGL], and 29 with familial partial lipodystrophy [FPLD]). An age- and gender-matched control group with a ratio of 1:2 was generated., Results: Patients with CGL had severely depleted mesenteric adipose tissue (2.0 [IQR: 1.5-3.5] mm vs. 18.8 [IQR: 4.4-42.2] mm in FPLD, P < .001; 30.3 [IQR: 13.9-46.6] mm in controls, P < .001) and retroperitoneal adipose tissue (1.3 [IQR: 0.0-5.3] mm vs. 33.7 [IQR: 21.6-42.1] mm in FPLD, P < .001; 29.7 [IQR: 23.1-36.7] mm in controls, P < .001). The AOM distance was shorter in patients with CGL (8.1 [IQR: 6.0-10.8] mm) compared to patients with FPLD (vs. 13.0 [IQR: 8.8-18.1] mm; P = .023) and controls (vs. 11.3 [IQR: 8.4-15.5] mm, P = .016). Leptin levels were positively correlated with AOM distance in lipodystrophy (r = .513, P < .001). Multivariate linear regression analysis identified body mass index as a significant predictor of AOM distance (data controlled for age and sex; beta = 0.537, 95% CI: 0.277-0.798, P < .001). Twelve of 19 patients (63%) with CGL had an AOM distance of < 10 mm, a risk factor that may predispose patients to developing superior mesenteric artery syndrome., Conclusion: CGL is associated with a severe loss of mesenteric adipose tissue, which leads to a narrowing of the space between the superior mesenteric artery and the aorta., (© 2024. The Author(s).)