Peroxisomal Multifunctional Protein 2 Is Essential for Lipid Homeostasis in Sertoli Cells and Male Fertility in Mice

Huyghe, Steven; Schmalbruch, Henning; Gendt, Karel De; Verhoeven, Guido; Guillou, Florian; Veldhoven, Paul P. Van; Baes, Myriam

doi:10.1210/en.2005-1571

Cited by 73 publications

(60 citation statements)

References 57 publications

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“…These observations suggest that Sertoli cells predominantly use lipids to produce ATP through catabolism of LCFAs. The result is in agreement with a recent report that the lipid droplets in Sertoli cells mainly consist of LCFAs (Huyghe et al 2006). The LCFAs are major energy substrates of cells (Crass 1972, 1977, Saddik & Lopaschuk 1991, Klaus 2004.…”

Section: Discussionsupporting

confidence: 93%

Apoptotic spermatogenic cells can be energy sources for Sertoli cells

Xiong¹,

Wang²,

Wu³

et al. 2009

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Apoptotic spermatogenic cells and residual bodies are phagocytosed and degraded by Sertoli cells during mammalian spermatogenesis. The meaning of this event remains to be clarified. In this report, we demonstrate that apoptotic spermatogenic cells and residual bodies can be used to produce ATP by Sertoli cells after phagocytosis of them. Sertoli cells produced the highest level of ATP compared with other testicular cells. Phagocytosis assay in vitro showed that engulfment of apoptotic spermatogenic cells increases ATP production by Sertoli cells. The increased ATP production was detected in seminiferous tubules at the stages where phagocytosis occurs. Induced apoptosis of spermatogenic cells in vivo increased ATP production in seminiferous tubules. The augmentation of ATP production both in vitro and in vivo associated with the lipid formation in Sertoli cells after phagocytosis of apoptotic spermatogenic cells. The lipid b-oxidation was a predominant pathway to produce ATP in Sertoli cells. We conclude that after phagocytosis by Sertoli cells, apoptotic spermatogenic cells are degraded to form lipids that are then used to produce ATP. The results suggest that apoptotic spermatogenic cells can be energy sources for Sertoli cells that may define a novel meaning of spermatogenic cell death.

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Section: Discussionsupporting

confidence: 93%

Apoptotic spermatogenic cells can be energy sources for Sertoli cells

Xiong¹,

Wang²,

Wu³

et al. 2009

Reproduction

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“…Abnormal lipid droplets are observed in hepatocytes and neurons in human patients with DBP deficiency, and it has been suggested that male sterility in a knock-out mouse model correlated with the appearance of large lipid droplets in the testes (38)(39)(40). We propose that common factors in mammalian and C. elegans diets contribute to lipid droplet expansion in mutants with peroxisomal defects.…”

Section: Discussionmentioning

confidence: 76%

Genetic and dietary regulation of lipid droplet expansion in Caenorhabditis elegans

Zhang

Box

et al. 2010

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

146

180

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Dietary fat accumulates in lipid droplets or endolysosomal compartments that undergo selective expansion under normal or pathophysiological conditions. We find that genetic defects in a peroxisomal β-oxidation pathway cause size expansion in lipid droplets that are distinct from the lysosome-related organelles in Caenorhabditis elegans. Expansion of lipid droplets is accompanied by an increase in triglycerides (TAG) that are resistant to fasting-or TAG lipase-triggered lipolysis. Nevertheless, in mutant animals, a diet poor in vaccenic acid reduced the TAG level and lipid droplet size. Our results implicate peroxisomal dysfunction in pathologic lipid droplet expansion in animals and illustrate how dietary factors modulate the phenotype of such genetic defects.peroxisome | β-oxidation | daf-22 | dhs-28 | maoc-1

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“…For calculation, the areas corresponding to the eluted nitrophenylhydrazone derivatives of hexadecanal, octadecanal, and octadecenal were summed up and compared with an external standard (gravimetric solution of hexadecanal dimethyl acetal). Triglycerides, cholesterol, and cholesterylesters were isolated by thin-layer chromatography and analyzed with coupled enzymatic assays as described previously Huyghe et al, 2006a) except for cholesterylesters and triglycerides that were hydrolyzed chemically (5% 5 M KOH in ethanol; 75°C; 90 min). Statistical analysis was done by unpaired Student's t test.…”

Section: Biochemical Analysismentioning

confidence: 99%

Absence of Functional Peroxisomes from Mouse CNS Causes Dysmyelination and Axon Degeneration

Hulshagen¹,

Krysko²,

Bottelbergs³

et al. 2008

J. Neurosci.

100

110

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Peroxisomal metabolism is essential for normal brain development both in men and in mice. Using conditional knock-out mice, we recently showed that peroxisome deficiency in liver has a severe and persistent impact on the formation of cortex and cerebellum, whereas absence of functional peroxisomes from the CNS only causes developmental delays without obvious alteration of brain architecture.We now report that a substantial fraction of the latter Nes-Pex5 knock-out mice survive into adulthood but develop progressive motoric and coordination problems, impaired exploration, and a deficit in cognition and die before the age of 6 months. Histopathologically, both the white and gray matter of the CNS displayed a region-specific accumulation of neutral lipids, astrogliosis and microgliosis, upregulation of catalase, and scattered cell death. Nes-Pex5 knock-out mice featured a dramatic reduction of myelin staining in corpus callosum, whereas cerebellum and other white matter tracts were less affected or unchanged. This was accompanied by a depletion of alkenylphospholipids in myelin and differentially reduced immunoreactivity of myelin proteins. EM analysis revealed that myelin wrappings around axons did still form, but they showed a reduction in thickness relative to axon diameters. Remarkably, multifocal axonal damage occurred in the corpus callosum. Thereby, debris accumulated between axolemma and inner myelin surface and axons collapsed, although myelin sheaths remained present. These anomalies of myelinated axons were already present in juvenile mice but aggravated in adulthood. Together, loss of CNS peroxisomal metabolism both affects myelin sheaths and axonal integrity possibly via independent pathways.

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Peroxisomal Multifunctional Protein 2 Is Essential for Lipid Homeostasis in Sertoli Cells and Male Fertility in Mice

Cited by 73 publications

References 57 publications

Apoptotic spermatogenic cells can be energy sources for Sertoli cells

Apoptotic spermatogenic cells can be energy sources for Sertoli cells

Genetic and dietary regulation of lipid droplet expansion in Caenorhabditis elegans

Absence of Functional Peroxisomes from Mouse CNS Causes Dysmyelination and Axon Degeneration

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