Targeted disruption of steroidogenic acute regulatory protein D4 leads to modest weight reduction and minor alterations in lipid metabolism

Riegelhaupt, Joshua; Waase, Marc; Garbarino, Jeanne; Cruz, Daniel; Breslow, Jan L.

doi:10.1194/jlr.m003095

Cited by 46 publications

(30 citation statements)

References 35 publications

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“…Therefore, such proteins appear to be confined to the cytoplasm, where they bind insoluble lipids, permitting their transport across aqueous cytosol. StarD4 and StarD5 have been proposed to play a role in the movement of cholesterol from intracellular lipid droplets to the OMM ( 48 ). Surprisingly, StarD4 knockout mice display no disruption of steroidogenesis and only minor alterations in lipid metabolism.…”

Section: Steroidogenesismentioning

confidence: 99%

Hedgehog Signaling and Steroidogenesis

Finco

LaPensee²,

Krill

et al. 2015

Annu. Rev. Physiol.

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Since its discovery nearly 30 years ago, the Hedgehog (Hh) signaling pathway has been shown to be pivotal in many developmental and pathophysiological processes in several steroidogenic tissues, including the testis, ovary, adrenal cortex, and placenta. New evidence links the evolutionarily conserved Hh pathway to the steroidogenic organs, demonstrating how Hh signaling can influence their development and homeostasis and can act in concert with steroids to mediate physiological functions. In this review, we highlight the role of the components of the Hh signaling pathway in steroidogenesis of endocrine tissues.

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Section: Steroidogenesismentioning

confidence: 99%

Hedgehog Signaling and Steroidogenesis

Finco

LaPensee²,

Krill

et al. 2015

Annu. Rev. Physiol.

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“…Finally, the upregulation of Stard4 and Stard5 could make the metabolism of cholesterol more efficient by regulating the transfer of cholesterol to different cellular compartments. Apart from that, by binding, transporting, and positioning dietary cholesterol, STARD4 protein increases cholesteryl ester formation and is, therefore, postulated to play a role in the determination of serum total cholesterol and LDL-cholesterol (Riegelhaupt et al 2010), which were found to be significantly decreased in serum of HF-DR mice (Fig. 3).…”

Section: Induction Of Mitophagymentioning

confidence: 99%

Dietary restriction of mice on a high-fat diet induces substrate efficiency and improves metabolic health

Duivenvoorde¹,

Schothorst²,

Bunschoten³

et al. 2011

Journal of Molecular Endocrinology

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High energy intake and, specifically, high dietary fat intake challenge the mammalian metabolism and correlate with many metabolic disorders such as obesity and diabetes. However, dietary restriction (DR) is known to prevent the development of metabolic disorders. The current western diets are highly enriched in fat, and it is as yet unclear whether DR on a certain high-fat (HF) diet elicits similar beneficial effects on health. In this research, we report that HF-DR improves metabolic health of mice compared with mice receiving the same diet on an ad libitum basis (HF-AL). Already after five weeks of restriction, the serum levels of cholesterol and leptin were significantly decreased in HF-DR mice, whereas their glucose sensitivity and serum adiponectin levels were increased. The body weight and measured serum parameters remained stable in the following 7 weeks of restriction, implying metabolic adaptation. To understand the molecular events associated with this adaptation, we analyzed gene expression in white adipose tissue (WAT) with whole genome microarrays. HF-DR strongly influenced gene expression in WAT; in total, 8643 genes were differentially expressed between both groups of mice, with a major role for genes involved in lipid metabolism and mitochondrial functioning. This was confirmed by quantitative real-time reverse transcription-PCR and substantiated by increase in mitochondrial density in WAT of HF-DR mice. These results provide new insights in the metabolic flexibility of dietary restricted animals and suggest the development of substrate efficiency.

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“…Because StarD4 and StarD5 resemble a StAR molecule lacking its mitochondrial leader peptide and because such leaderless StAR molecules are fully active in transfected cells ( 144,181 ) it seemed that StarD4 and/or StarD5 might function to "load" cholesterol into the OMM, where it could be acted upon by StAR itself. However, knockout of StarD4 in the mouse resulted in minimal changes in weight and serum lipids and no changes in steroidogenesis, so that any role played by StarD4 appears to be compensated by other factors ( 182 ). Human disorders of the StarD proteins, other than StAR itself (see below), have not been reported.…”

Section: Transport Of Cholesterol To Mitochondria: Cholesterol-bindinmentioning

confidence: 99%