Saturated free fatty acids, palmitic acid and stearic acid, induce apoptosis by stimulation of ceramide generation in rat testicular Leydig cell

Lü, Zhaohui; Mu, Yiming; Wang, Baoan; Li, Xie-Ling; Lu, Juming; Li, Jiangyuan; Pan, Changyu; Yanase, Toshihiko; Nawata, Hajime

doi:10.1016/s0006-291x(03)00449-2

Cited by 116 publications

(88 citation statements)

References 19 publications

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“…Similar toxic effects of NEFA have also been described for Leydig cells, muscle cells and pancreatic b-cells, and it is the induction of apoptosis and/or insulin resistance as well as changes in membrane properties that have been specifically suggested as potential mechanisms for explaining the observed toxic effects (Shimabukuro et al, 1998;Leroy, Van Soom, Opsomer and Bols Maedler et al, 2001;Hirabara et al, 2003;Lu et al, 2003;Jorritsma et al, 2004).…”

Section: Introductionmentioning

confidence: 66%

The consequences of metabolic changes in high-yielding dairy cows on oocyte and embryo quality

Leroy

Soom

Opsomer

et al. 2008

Animal

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Unsatisfactory reproductive performance in dairy cows, such as reduced conception rates, in addition to an increased incidence of early embryonic mortality, is reported worldwide and has been associated with a period of negative energy balance (NEB) early post partum. Typically, NEB is associated with biochemical changes such as high non-esterified fatty acid (NEFA), high b-hydroxybutyrate (b-OHB) and low glucose concentrations. The concentrations of these and other metabolites in the follicular fluid (FF) of high-yielding dairy cows during NEB were determined and extensively analyzed, and then were replicated in in vitro maturation models to investigate their effect on oocyte quality. The results showed that typical metabolic changes during NEB are well reflected in the FF of the dominant follicle. However, the oocyte seems to be relatively isolated from extremely elevated NEFA or very low glucose concentrations in the blood. Nevertheless, the in vitro maturation models revealed that NEB-associated high NEFA and low glucose levels in the FF are indeed toxic to the oocyte, resulting in deficient oocyte maturation and developmental competence. Induced apoptosis and necrosis in the cumulus cells was particularly obvious. Furthermore, maturation in saturated free fatty acid-rich media had a carry-over effect on embryo quality, leading to reduced cryotolerance of day 7 embryos. Only b-OHB showed an additive toxic effect in moderately hypoglycemic maturation conditions. These in vitro maturation models, based on in vivo observations, suggest that a period of NEB may hamper the fertility of high-yielding dairy cows through increased NEFA and decreased glucose concentrations in the FF directly affecting oocyte quality. In addition to oocyte quality, these results also demonstrate that embryo quality is reduced following an NEB episode. This important observation may be linked to the typical diet provided to stimulate milk yield, or to physiological adaptations sustaining the high milk production. Research into this phenomenon is ongoing.

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Section: Introductionmentioning

confidence: 66%

The consequences of metabolic changes in high-yielding dairy cows on oocyte and embryo quality

Leroy

Soom

Opsomer

et al. 2008

Animal

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“…Both AMPK and cAMP/PKA are involved as signaling pathways. Palmitate induces apoptosis in diverse cell types such as endothelial cells (Yamaguchi et al 2002), cardiomyocytes (Sparagna et al 2000), pancreatic b-cells (Kwon et al 2004), testicular Leydig cells (Lu et al 2003), human granulosa cells (Mu et al 2001), bovine retinal pericytes (Cacicedo et al 2005), skeletal muscle myotubes (Turpin et al 2006), and human osteoblast cells (Kim et al 2008b). …”

Section: Discussionmentioning

confidence: 99%

Adiponectin inhibits palmitate-induced apoptosis through suppression of reactive oxygen species in endothelial cells: involvement of cAMP/protein kinase A and AMP-activated protein kinase

Kim¹,

Song²,

Kim³

et al. 2010

Journal of Endocrinology

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The present study examined whether adiponectin can inhibit palmitate-induced apoptosis, and also the associated mechanisms and signal transduction pathways in human umbilical vein endothelial cells. Cells treated with 500 mM palmitate for 48 h increased reactive oxygen species (ROS) generation and induced apoptosis. Treatment with antioxidant N-acetyl-L-cysteine (1 mM) and globular adiponectin (5 mg/ml) inhibited palmitate-induced ROS generation and apoptosis. The AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-b-D-ribofuranoside (AICAR; 1 mM), and cAMP activators forskolin (10 mM) and cholera toxin (200 ng/ml) also displayed the same effects. The inhibitory effects of adiponectin on ROS generation and apoptosis were reversed by the AMPK inhibitor compound C (40 mM), cAMP inhibitor SQ22536 (50 mM), and protein kinase A (PKA) inhibitor H-89 (10 mM). The inhibitory effect of forskolin on palmitateinduced apoptosis was reversed by compound C, whereas the inhibitory effect of AICAR was not reversed by SQ22536 and H-89. AICAR and forskolin could not inhibit palmitate-induced apoptosis in cells treated with dominantnegative AMPK. Forskolin increased phosphorylated AMPK at both Thr-172 and Ser-485/491. These results suggest that adiponectin inhibits palmitate-induced apoptosis by suppression of ROS generation via both the cAMP/PKA and AMPK pathways. Interaction between cAMP/PKA and AMPK pathways may be involved.

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“…Interestingly, in rats, elevated NEFA concentrations for 48 h can decrease insulin secretion by the β-cells of the pancreatic islets in response to a glucose challenge [123]. Moreover, NEFA are cytotoxic for several cell types [124][125][126][127], including bovine granulosa and theca cells [128,129]. So (prolonged) exposure to high NEFA concentrations during periods of NEB may hamper follicle growth and development, disrupting the complex endocrine system and promoting the formation of ovarian cysts.…”

Section: Predisposing Factors For Cofmentioning

confidence: 99%

Aetiology and pathogenesis of cystic ovarian follicles in dairy cattle: a review

2006

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-Cystic ovarian follicles (COF) are an important ovarian dysfunction and a major cause of reproductive failure in dairy cattle. Due to the complexity of the disorder and the heterogeneity of the clinical signs, a clear definition is lacking. A follicle becomes cystic when it fails to ovulate and persists on the ovary. Despite an abundance of literature on the subject, the exact pathogenesis of COF is unclear. It is generally accepted that disruption of the hypothalamo-pituitary-gonadal axis, by endogenous and/or exogenous factors, causes cyst formation. Secretion of GnRH/LH from the hypothalamus-pituitary is aberrant, which is attributed to insensitivity of the hypothalamus-pituitary to the positive feedback effect of oestrogens. In addition, several factors can influence GnRH/LH release at the hypothalamo-pituitary level. At the ovarian level, cellular and molecular changes in the growing follicle may contribute to anovulation and cyst formation, but studying follicular changes prior to cyst formation remains extremely difficult. Differences in receptor expression between COF and dominant follicles may be an indication of the pathways involved in cyst formation. The genotypic and phenotypic link of COF with milk yield may be attributed to negative energy balance and the associated metabolic and hormonal adaptations. Altered metabolite and hormone concentrations may influence follicle growth and cyst development, both at the level of the hypothalamus-pituitary and the ovarian level.cystic ovarian follicles / pathogenesis / hypothalamus-pituitary / ovary / negative energy balance

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Saturated free fatty acids, palmitic acid and stearic acid, induce apoptosis by stimulation of ceramide generation in rat testicular Leydig cell

Cited by 116 publications

References 19 publications

The consequences of metabolic changes in high-yielding dairy cows on oocyte and embryo quality

The consequences of metabolic changes in high-yielding dairy cows on oocyte and embryo quality

Adiponectin inhibits palmitate-induced apoptosis through suppression of reactive oxygen species in endothelial cells: involvement of cAMP/protein kinase A and AMP-activated protein kinase

Aetiology and pathogenesis of cystic ovarian follicles in dairy cattle: a review

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