Insulin Resistance Is a Sufficient Basis for Hyperandrogenism in Lipodystrophic Women with Polycystic Ovarian Syndrome

Lungu, Andreea O.; Zadeh, Elika Safar; Goodling, Anne; Cochran, Elaine; Görden, Phillip

doi:10.1210/jc.2011-1896

Cited by 53 publications

(24 citation statements)

References 25 publications

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“…Among the female patients, only three patients had primary/secondary amenorrhea including our case [10,13,17], whereas the others reported a regular menstrual cycle. Insulin is thought to stimulate ovarian thecal cells or stromal cells to produce androgen and decrease the production of SHBG by the liver, resulting in a hyperandrogenism [35][36][37]. Therefore, the characteristics of our patient support the view that the primary role of sustained hyperinsulinemia may be as a cause of secondary PCOS, acanthosis nigricans, and hirsutism [35,38,39].…”

Section: Discussionsupporting

confidence: 64%

Definitive diagnosis of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome caused by a recurrent de novo mutation in the POLD1 gene

et al. 2018

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Section: Discussionsupporting

confidence: 64%

Definitive diagnosis of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome caused by a recurrent de novo mutation in the POLD1 gene

et al. 2018

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“…22,23 More importantly, white adipocytes contain a giant unilocular LD, and the sizes of LDs in adipocytes reflect the lipid storage capacity and have been linked to the development of obesity and insulin resistance. 9,[24][25][26] Genetic screens in Drosophila and yeast cells have uncovered links between factors involved in phospholipid synthesis, 27,28 vesicular transport, 29,30 and seipin/Fldp 28,31,32 and regulation of LD size and morphology. However, the mechanisms of LD…”

Section: Cide Proteins In Lipid Storage and Ld Growthmentioning

confidence: 99%

CIDE Proteins and Lipid Metabolism

Zhou²,

Li³

2012

ATVB

144

110

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Abstract-Lipid homeostasis is maintained through the coordination of lipid metabolism in various tissues, including adipose tissue and the liver. The disruption of lipid homeostasis often results in the development of metabolic disorders such as obesity, diabetes mellitus, liver steatosis, and cardiovascular diseases. Cell death-inducing DNA fragmentation factor 45-like effector family proteins, including Cidea, Cideb, and Fsp27 (Cidec), are emerging as important regulators of various lipid metabolic pathways and play pivotal roles in the development of metabolic disorders. This review summarizes the latest cell death-inducing DNA fragmentation factor 45-like effector protein discoveries related to the control of lipid metabolism, with emphasis on the role of these proteins in lipid droplet growth in adipocytes and in the regulation of very low-density lipoprotein lipidation and maturation in hepatocytes.

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“…The LD fraction fl oated on the top was is the main site of neutral lipid storage in all cell types ( 14,15 ). Recently, the LD has been recognized as a dynamic and functionally active organelle that regulates protein traffi cking, viral assembly, and insulin sensitivity (16)(17)(18)(19)(20). Two types of LDs, cytosolic LDs and ER-associated lumenal LDs, have been identifi ed ( 21,22 ).…”

Section: Subcellular Fractionation and Analysis Of Microsomal Lumenalmentioning

confidence: 99%

Opposing roles of cell death-inducing DFF45-like effector B and perilipin 2 in controlling hepatic VLDL lipidation

Zhou

et al. 2012

Journal of Lipid Research

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triglycerides (TAG) and cholesterol and for the development of metabolic disorders, including obesity, diabetes, and hepatic steatosis. It is believed that VLDL assembly and maturation involves two steps ( 1, 2 ). The fi rst step is the formation of lipid-poor pre-VLDL particles involving the cotranslational lipidation of apolipoprotein B (apoB) with a few lipids, aided by microsomal triglyceride transfer protein (MTP) ( 3, 4 ). The second step is the transfer of large quantities of lipids, likely from TAG-rich lipid droplets (LD), to the pre-VLDL particles, converting the pre-VLDL particles into lipid-rich, mature VLDL particles ( 2-5 ). Thus far, the subcellular site of the addition of bulk lipids to pre-VLDL particles, the source of the lipids, and the factors promoting VLDL lipidation remain unclear. The endoplasmic reticulum (ER) has been suggested as the VLDL lipidation site because the majority of TAG is synthesized in the ER, and apoB-100 has been shown to be localized to the ER membrane ( 2, 6, 7 ). Others believe that the pre-VLDL particles are assembled in the ER and then exit, with the fi nal VLDL lipidation and maturation occurring primarily within the Golgi apparatus or post-ER compartments ( 8-11 ). For example, the biochemical separation of the lipoprotein particles from McA-RH7777 cells indicated that mature VLDL particles accumulate in the Golgi but not in the ER fractions ( 11,12 ). In addition, the late addition of bulk lipids to pre-VLDL particles is independent of both MTP activity and new triglyceride synthesis ( 12, 13 ).The availability of neutral lipids and the capacity to transfer TAG to pre-VLDL particles are crucial for VLDL lipidation and maturation. The LD, a subcellular organelle, Abstract Regulation of hepatic very low density lipoprotein (VLDL) assembly and maturation is crucial in controlling lipid homeostasis and in the development of metabolic disorders, including obesity, hepatic steatosis, and insulin resistance. Cideb, a member of cell death-inducing DFF45-like effector (CIDE) protein family, has been previously shown to promote VLDL lipidation and maturation. However, the precise subcellular location of Cideb-mediated VLDL lipidation and the factors modulating its activity remain elusive. In addition to its localization to endoplasmic reticulum (ER) and lipid droplets (LD), we observed that Cideb was also localized to the Golgi apparatus. Mature and lipid-rich VLDL particles did not accumulate in the Golgi apparatus in Cideb ؊ / ؊ livers. Interestingly, we observed that hepatic perilipin 2/adipose differentiation-related protein (ADRP) levels were markedly increased in Cideb ؊ / ؊ mice. Liver-specifi c knockdown of perilipin 2 in Cideb ؊ / ؊ mice resulted in the reduced accumulation of hepatic triglycerides (TAG), increased VLDL-TAG secretion, and the accumulation of mature TAG-rich VLDL in the Golgi apparatus. These data reveal that Cideb and perilipin 2 play opposing roles in controlling VLDL lipidation and hepatic lipid homeostasis. China,

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Insulin Resistance Is a Sufficient Basis for Hyperandrogenism in Lipodystrophic Women with Polycystic Ovarian Syndrome

Abstract: In the present study, we show that LD may be a model for the common forms of PCOS and that the endocrine features are corrected by leptin therapy, which reduces insulin resistance.

Cited by 53 publications

References 25 publications

Definitive diagnosis of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome caused by a recurrent <i>de novo</i> mutation in the <i>POLD1</i> gene

Definitive diagnosis of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome caused by a recurrent <i>de novo</i> mutation in the <i>POLD1</i> gene

CIDE Proteins and Lipid Metabolism

Opposing roles of cell death-inducing DFF45-like effector B and perilipin 2 in controlling hepatic VLDL lipidation

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