The molecular basis of genetic lipodystrophies

Bhayana, Shelly; Hegele, Robert A.

doi:10.1016/s0009-9120(02)00297-7

Cited by 22 publications

(18 citation statements)

References 73 publications

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“…While † Author for correspondence, University of California, Department of Nutritional Sciences & Toxicology, Berkeley, CA 94720, USA, adipocyte number has been shown to increase (hyperplasia) in morbid obesity, obesity is primarily attributed to adipocyte hypertrophy that occurs when TAG synthesis (esterification) exceeds TAG breakdown (lipolysis), resulting in elevated TAG storage [1]. Although it has been postulated that large adipocyte size may contribute to insulin resistance, the molecular mechanism is not clear.Paradoxically, the metabolic abnormalities typically found in obesity are also associated with lipodystrophies that are characterized by selective loss of adipose tissue from particular regions of the body [3][4][5][6]. Although the underlying molecular mechanisms are not clear, metabolic complications may result from ectopic storage of TAG in tissues such as the liver and muscle [7][8][9].…”

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“…Paradoxically, the metabolic abnormalities typically found in obesity are also associated with lipodystrophies that are characterized by selective loss of adipose tissue from particular regions of the body [3][4][5][6]. Although the underlying molecular mechanisms are not clear, metabolic complications may result from ectopic storage of TAG in tissues such as the liver and muscle [7][8][9].…”

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Triacylglycerol Metabolism In Adipose Tissue

et al. 2007

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Triacylglycerol (TAG) in adipose tissue serves as the major energy storage form in higher eukaryotes. Obesity, resulting from excess white adipose tissue, has increased dramatically in recent years resulting in a serious public health problem. Understanding of adipocyte-specific TAG synthesis and hydrolysis is critical to the development of strategies to treat and prevent obesity and its closely associated diseases, for example, Type 2 diabetes, hypertension and atherosclerosis. In this review, we present an overview of the major enzymes in TAG synthesis and lipolysis, including the recent discovery of a novel adipocyte TAG hydrolase. Keywords1-acylglycerol-3-phosphate acyltransferase; desnutrin/adipose triglyceride lipase; diacylglycerol acyltransferase; glycerol-3-phosphate acyltransferase; hormone-sensitive lipase; lipolysis; phosphatidic acid phosphatase; triacylglycerol White adipose tissue (WAT) is the major energy reserve in higher eukaryotes. The primary purposes of WAT are synthesis and storage of triacylglycerol (TAG) in periods of energy excess, and hydrolysis of TAG to generate fatty acids for use by other organs during periods of energy deprivation [1]. Adipose tissue also secretes adipokines that regulate energy intake and metabolism.The prevalence of obesity resulting from excess WAT has increased dramatically in recent years resulting in a serious public health problem, since obesity is closely associated with a number of disorders including Type 2 diabetes, hypertension and atherosclerosis [2]. While † Author for correspondence, University of California, Department of Nutritional Sciences & Toxicology, Berkeley, CA 94720, USA, adipocyte number has been shown to increase (hyperplasia) in morbid obesity, obesity is primarily attributed to adipocyte hypertrophy that occurs when TAG synthesis (esterification) exceeds TAG breakdown (lipolysis), resulting in elevated TAG storage [1]. Although it has been postulated that large adipocyte size may contribute to insulin resistance, the molecular mechanism is not clear.Paradoxically, the metabolic abnormalities typically found in obesity are also associated with lipodystrophies that are characterized by selective loss of adipose tissue from particular regions of the body [3][4][5][6]. Although the underlying molecular mechanisms are not clear, metabolic complications may result from ectopic storage of TAG in tissues such as the liver and muscle [7][8][9]. A proper capacity for TAG storage in adipocytes is clearly important for normal metabolic regulation. In view of the wide range of health problems associated with improper fat storage and release, it is critical to understand adipocyte-specific regulation of TAG synthesis and hydrolysis. Biosynthesis of triacylglycerolThe synthesis of phosphatidic acid and its subsequent conversion to TAG was described more than 40 years ago by Kennedy and coworkers [10], and is summarized in Figure 1. The initial committal step in this pathway is the formation of lysophosphatidic acid (1-acylglycerol-3-phosphate)...

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Triacylglycerol Metabolism In Adipose Tissue

et al. 2007

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“…For instance, in Ͼ90% of subjects with Dunnigan-type familial partial lipodystrophy (FPLD2; MIM 151660), the mutation in LMNA involves codon 482, and each mutation affects the sequence encoding the lamin A isoform. 6 Genetically modified mice have provided insights into the possible pathogenic mechanisms of LMNA mutations. For instance, monocytes from Lmnadeficient mice showed displaced fragmented heterochromatin and disorganized, detached desmin filaments.…”

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Laminopathies and Atherosclerosis

Alshali

Hegele

2004

ATVB

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Abstract-Laminopathies are genetic diseases that encompass a wide spectrum of phenotypes with diverse tissue pathologies and result mainly from mutations in the LMNA gene encoding nuclear lamin A/C. Some laminopathies affect the cardiovascular system, and a few (namely, Dunnigan-type familial partial lipodystrophy [FPLD2] and HutchinsonGilford progeria syndrome [HGPS]) feature atherosclerosis as a key component. The premature atherosclerosis of FPLD2 is probably related to characteristic proatherogenic metabolic disturbances such as dyslipidemia, hyperinsulinemia, hypertension, and diabetes. In contrast, the premature atherosclerosis of HGPS occurs with less exposure to metabolic proatherogenic traits and probably reflects the generalized process of accelerated aging in HGPS. Although some common polymorphisms of LMNA have been associated with traits related to atherosclerosis, the monogenic diseases Key Words: nuclear envelope Ⅲ insulin resistance Ⅲ aging Ⅲ vascular disease Ⅲ progeria T he nuclear lamina is a 20-nm filamentous meshwork that underlies the inner nuclear membrane and plays a central role in defining interphase nuclear architecture, DNA replication, and chromatin organization. 1 Nuclear lamins are type V intermediate filaments that are the major components of the nuclear lamina.

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“…Leptin deficiency, caused by the absence of adipose tissue, could be an important determinant of the metabolic abnormalities. (6).…”

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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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The molecular basis of genetic lipodystrophies

Cited by 22 publications

References 73 publications

Triacylglycerol Metabolism In Adipose Tissue

Triacylglycerol Metabolism In Adipose Tissue

Laminopathies and Atherosclerosis

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

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