Triglyceride-induced Diabetes Mellitus in Congenital Generalized Lipodystrophy

Montenegro, Renan Magalhães; Montenegro, Ana Paula Dias Rangel; Fernandes, Maria Inez Machado; Moraes, Renata Ribeiro De; Gouveia, L. M. F. B.; Elías, Jorge; Muglia, Valdair Francisco; Foss, Milton César; Moreira, Ayrton Custódio; Martinelli, Carlos Eduardo

doi:10.1515/jpem.2002.15.4.441

Cited by 14 publications

(10 citation statements)

References 10 publications

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“…Restriction of caloric intake in 740 kcal/day combined with reduction of total dietary fat and partial substitution of dietary medium-chain triglycerides (MCT) for longchain triglycerides (LCT) for 6 months was associated with improved plasma glucose and triglyceride levels in a pediatric patient with CGL [38]. Analogous findings were independently reported by others [7,34].…”

Section: Nutritional Interventions In the Management Of Lipodystrophysupporting

confidence: 58%

Lipodystrophies: adipose tissue disorders with severe metabolic implications

Cortés

Fernández‐Galilea

2015

J Physiol Biochem

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Lipodystrophy encompass a group of heterogeneous disorders consisting in marked reduction, absence, and/or the redistribution of adipose tissue. Lipodystrophy is frequently complicated with severe insulin resistance, diabetes, hyperlipidemia, and fatty liver. Anatomically, lipodystrophies can be partial or generalized. Etiologically, they can be congenital or acquired. Lipodystrophy diagnosis can be challenging, and it has been suggested that partial forms can be easily misdiagnosed as common central obesity with associated metabolic syndrome. Conventional insulin-sensitizing approaches usually fail to fully ameliorate insulin resistance in lipodystrophic patients. Leptin replacement is an approved therapy for the metabolic complications of congenital generalized lipodystrophy. Novel nutritional interventions are promising complementary approaches for treating lipodystrophy metabolic complications.

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Section: Nutritional Interventions In the Management Of Lipodystrophysupporting

confidence: 58%

Lipodystrophies: adipose tissue disorders with severe metabolic implications

Cortés

Fernández‐Galilea

2015

J Physiol Biochem

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“…In CGL, normally the adipose deficiency is accompanied by severe insulin resistance, hyperinsulinemia, hyperglycemia, hypertriglyceridemia, and fatty liver, which persists throughout life (24). Although the neonatal phenotype mirrors CGL, adult mice overcome the fatty liver and hyperlipidemia and are only mildly glucose intolerant, which is distinct from most other lipodystrophy models (25)(26)(27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

Compensation by the muscle limits the metabolic consequences of lipodystrophy in PPARγ hypomorphic mice

Koutníková

Cock

Watanabe

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

174

143

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Peroxisome proliferator-activated receptor ␥ (PPAR␥) is a nuclear receptor, which controls adipocyte differentiation. We targeted with homologous recombination the PPAR␥2-specific exon B, resulting in a white adipose tissue knockdown of PPAR␥. Although homozygous (PPAR␥ hyp/hyp ) mice are born with similar weight as the WT mice, the PPAR␥ hyp/hyp animals become growth retarded and develop severe lipodystrophy and hyperlipidemia. Almost half of these PPAR␥ hyp/hyp mice die before adulthood, whereas the surviving PPAR␥ hyp/hyp animals overcome the growth retardation, yet remain lipodystrophic. In contrast to most lipodystrophic models, the adult PPAR␥ hyp/hyp mice only have mild glucose intolerance and do not have a fatty liver. These metabolic consequences of the lipodystrophy are relatively benign because of the induction of a compensatory gene expression program in the muscle that enables efficient oxidation of excess lipids. The PPAR␥ hyp/hyp mice unequivocally demonstrate that PPAR␥ is the master regulator of adipogenesis in vivo and establish that lipid and glucose homeostasis can be relatively well maintained in the absence of white adipose tissue.T he peroxisome proliferator-activated receptor ␥ (PPAR␥) is a nuclear receptor that acts as a lipid sensor, integrating the control of energy, lipid, and glucose homeostasis (1). The actions of PPAR␥ are mediated by two protein isoforms, the widely expressed PPAR␥1 and adipose tissue-restricted PPAR␥2 with an additional 28 aa in the NH 2 terminus (2-4). PPAR␥ is the master regulator of differentiation and energy storage by adipocytes (5-8). Despite undisputed arguments that support a pivotal role of PPAR␥ in adipocyte differentiation in vitro, the PPAR␥ field has been slowed by the absence of good animal models for PPAR␥ deficiency, because homozygous PPAR␥-deficient animals are embryonic lethal (8). This has had a restrictive impact on studies aimed at unraveling the pleiotropic roles of PPAR␥ in adult homeostasis. We therefore generated, by homologous recombination, mice that carry a hypomorphic mutation at the PPAR␥2 locus and characterized the molecular and metabolic phenotype of these mice. MethodsHomologous Recombination. The main features of our targeting strategy are shown in Fig. 1A. The loxP sites were inserted in reverse orientation at position Ϫ45 of the PPAR␥2 gene, 445 bp downstream of the exon B splice site and at the 3Ј end of the frt-PGKneo-frt cassette. The Pro-12-Ala mutation that was introduced in the B exon was flanked by an EcoRI site. Chimeric animals were generated from two independently targeted embryonic stem (ES) cell clones (nos. 84 and 73). Heterozygous animals, derived from the two ES cell clones, were backcrossed for seven generations to mice with either a SV129 or a C5S7BL͞6J background and then intercrossed to generate PPAR␥ hyp/hyp mice for analysis. The Pro-12-Ala knock-in PPAR␥ Ala12Ala animals were generated by intercrossing PPAR␥ hyp/hyp mice with mice that expressed the FLP recombinase under the control of a cytomegalovirus ...

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“…Diet is the most important aspect of management of BSCL individuals. The carbohydrate intake should be restricted and diet of patients with hypertriglyceridemia should contain low fat and high medium chain triglycerides (MCT) (12). Metformin has been shown to have some effect in helping patients reduce their appetite and improve hepatic steatosis (13).…”

Section: Discussionmentioning

confidence: 99%

A very rare cause of acute pancreatitis: Berardinelli-Seip congenital lipodystrophy

İşlek

Sayar²,

Yılmaz³

et al. 2015

Turk J Gastroenterol

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Pancreatitis is among rare diseases in pediatrics clinics. It is usually presented with a sign of underlying systemic disease. Berardinelli-Seip congenital lipodystrophy (BSCL) is a very rare disease characterized by near absence of adipose tissue resulting in apparent muscle hypertrophy from birth or early infancy associated with severe insulin resistance. Common clinical features are hypertriglyceridemia, acanthosis nigricans, hepatomegaly with or without splenomegaly and high stature. Acromegaloid features, cardiomyopathy and mental retardation can also be present. We describe a 7-year-old Turkish boy with these clinical features of BSCL and presented with acute pancreatitis.

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Triglyceride-induced Diabetes Mellitus in Congenital Generalized Lipodystrophy

Cited by 14 publications

References 10 publications

Lipodystrophies: adipose tissue disorders with severe metabolic implications

Lipodystrophies: adipose tissue disorders with severe metabolic implications

Compensation by the muscle limits the metabolic consequences of lipodystrophy in PPARγ hypomorphic mice

A very rare cause of acute pancreatitis: Berardinelli-Seip congenital lipodystrophy

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