Alteration of mitochondrial oxidative capacity during porcine preadipocyte differentiation and in response to leptin

Luo, Guifen; Yu, Taiyong; Xu, Wen; Liu, Ying; Yang, Gongshe

doi:10.1007/s11010-007-9587-2

Cited by 25 publications

(30 citation statements)

References 30 publications

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“…This important difference in the total abundance of cellular ATP between preadipocytes and adipocytes might be explained most likely by the high ATP consumption of differentiated cells when compared with more metabolically quiescent preadipocytes. Although ATP content was found to be higher in preadipocytes than in adipocytes, this result is in agreement with previous data obtained for porcine adipocyte differentiation (46). Unexpectedly, the ATP content in adipocytes challenged with either TNF␣ or FCCP was not decreased after 1 day and is even transiently higher in cells treated for 3 days when compared with untreated adipocytes.…”

Section: Resultssupporting

confidence: 93%

Mild mitochondrial uncoupling does not affect mitochondrial biogenesis but downregulates pyruvate carboxylase in adipocytes: role for triglyceride content reduction

Pauw

Demine

Tejerina

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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De Pauw A, Demine S, Tejerina S, Dieu M, Delaive E, Kel A, Renard P, Raes M, Arnould T. Mild mitochondrial uncoupling does not affect mitochondrial biogenesis but downregulates pyruvate carboxylase in adipocytes: role for triglyceride content reduction. Am J Physiol Endocrinol Metab 302: E1123-E1141, 2012. First published February 21, 2012 doi:10.1152/ajpendo.00117.2011In adipocytes, mitochondrial uncoupling is known to trigger a triglyceride loss comparable with the one induced by TNF␣, a proinflammatory cytokine. However, the impact of a mitochondrial uncoupling on the abundance/composition of mitochondria and its connection with triglyceride content in adipocytes is largely unknown. In this work, the effects of a mild mitochondrial uncoupling triggered by FCCP were investigated on the mitochondrial population of 3T3-L1 adipocytes by both quantitative and qualitative approaches. We found that mild mitochondrial uncoupling does not stimulate mitochondrial biogenesis in adipocytes but induces an adaptive cell response characterized by quantitative modifications of mitochondrial protein content. Superoxide anion radical level was increased in mitochondria of both TNF␣-and FCCP-treated adipocytes, whereas mitochondrial DNA copy number was significantly higher only in TNF␣-treated cells. Subproteomic analysis revealed that the abundance of pyruvate carboxylase was reduced significantly in mitochondria of TNF␣-and FCCP-treated adipocytes. Functional study showed that overexpression of this major enzyme of lipid metabolism is able to prevent the triglyceride content reduction in adipocytes exposed to mitochondrial uncoupling or TNF␣. These results suggest a new mechanism by which the effects of mitochondrial uncoupling might limit triglyceride accumulation in adipocytes.adipocytes; carbonyl cyanide p-trifluoromethoxyphenylhydrazone; tumor necrosis factor-␣; mitoproteome OBESITY RESULTS LARGELY FROM A CHRONICALLY POSITIVE energy balance. Therefore, reducing body energy intake and increasing energy expenditure are two approaches that have been translated into strategies to limit fat accumulation. Because mitochondria play a critical role in the process of energy expenditure, the alteration of oxidative phosphorylation (OX-PHOS) efficiency through OXPHOS uncoupling from ATP production in white adipocytes has been considered as an attractive approach to fight obesity (7, 69). In other words, uncoupling increases cellular metabolic demand since uncoupling OXPHOS lowers ATP production and increases the demand for reducing equivalents to restore/maintain mitochondrial membrane potential, thereby increasing substrate catabolism, which would theoretically decrease triglyceride (TG) stores in adipocytes. Indeed, although mitochondrial dysfunction could represent a major cause of lipid metabolism disorders and pathological triglyceride accumulation in several cell lines (50, 75), we and others have shown that mitochondrial uncoupling in adipocytes triggers lipolysis, limits fatty acid synthesis, and leads to a reduction in TG ...

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Section: Resultssupporting

confidence: 93%

Mild mitochondrial uncoupling does not affect mitochondrial biogenesis but downregulates pyruvate carboxylase in adipocytes: role for triglyceride content reduction

Pauw

Demine

Tejerina

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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“…We also report that OLETF rats tended to express more triceps PGC-1α mRNA, which is a known regulator of FNDC5 gene expression. Given that: a) the obese OLETF animals exhibited greater circulating leptin, and b) leptin signaling can increase PGC1α mRNA expression [6–7], we hypothesized that an increase in PGC-1α and consequently, FNDC5 mRNA expression patterns occurred in an exercise-independent manner in the examined OLETF rats. Indeed, plasma leptin was positively correlated with triceps FNDC5 mRNA expression levels, as well as PGC1α mRNA expression.…”

Section: Discussionmentioning

confidence: 99%

Elevated skeletal muscle irisin precursor FNDC5 mRNA in obese OLETF rats

et al. 2013

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OBJECTIVE There is debate as to whether fibronectin type III domain containing 5 (FNDC5) and its protein product irisin are therapeutic targets for obesity-associated maladies. Thus, we sought to examine FNDC5 mRNA within skeletal muscle of obese/diabetic-prone Otsuka Long-Evans Tokushima Fatty (OLETF) rats versus lean/healthy Long Evans Tokushima Otsuka (LETO) rats. We hypothesized that FNDC5 expression would be greater in obese (OLETF) versus lean (LETO) animals. MATERIALS/METHODS Triceps muscle of 30–32 week old OLETF and LETO rats were assayed for FNDC5 and PGC1α mRNA levels. Body composition and circulating biomarkers of the OLETF and LETO rats were also correlated with skeletal muscle FNDC5 mRNA expression patterns in order to examine potential relationships that may exist. RESULTS OLETF rats exhibited twice the amount of triceps FNDC5 mRNA compared to LETO rats (p < 0.01). Significant positive correlations existed between triceps muscle FNDC5 mRNA expression patterns versus fat mass (r = 0.70, p = 0.008), as well as plasma leptin (r = 0.82, p < 0.001). PGC1α mRNA levels were also highly correlated with FNDC5 mRNA (r = 0.85, p < 0.001). In subsequent culture experiments, low and high physiological doses of leptin had no effect on PGC1α mRNA or FNDC5 mRNA levels in C2C12 myotubes. Paradoxically, circulating irisin concentrations tended to be higher in a second cohort of LETO versus OLETF rats (p = 0.085). CONCLUSION These results reveal a positive association between total body adiposity and skeletal muscle FNDC5 gene expression. Of interest, circulating irisin levels tended to be lower in OLETF rats. Further research is needed to examine whether other adipose tissue-derived factors up-regulate FNDC5 transcription and/or inhibit irisin biosynthesis from FNDC5.

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“…Functional linkages have been observed between leptin and UCP2 in peripheral tissues. For example, leptin diminished UCP2 abundance in pancreas but not brain during neonatal development (Gnanalingham et al 2005), whereas significant upregulation of UCP2 by leptin was observed in preadipocytes (Luo et al 2008). UCP2 was shown to promote fatty acid oxidation and limit glycolysis-derived pyruvate catabolism (Pecqueur et al .…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Uncoupling Protein-2 (UCP2) Mediates Leptin Protection Against MPP+ Toxicity in Neuronal Cells

Liu

et al. 2009

Neurotox Res

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Mitochondrial dysfunction is involved in the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD). Uncoupling proteins (UCPs) delink ATP production from biofuel oxidation in mitochondria to reduce oxidative stress. UCP2 is expressed in brain, and has neuroprotective effects under various toxic insults. We observed induction of UCP2 expression by leptin in neuronal cultures, and hypothesize that leptin may preserve neuronal survival via UCP2. We showed that leptin preserved cell survival in neuronal SH-SY5Y cells against MPP+ toxicity (widely used in experimental Parkinsonian models) by maintaining ATP levels and mitochondrial membrane potential (MMP); these effects were accompanied by increased UCP2 expression. Leptin had no effect in modulating reactive oxygen species levels. Stable knockdown of UCP2 expression reduced ATP levels, and abolished leptin protection against MPP+-induced mitochondrial depolarization, ATP deficiency, and cell death, indicating that UCP2 is critical in mediating these neuroprotective effects of leptin against MPP+ toxicity. Interestingly, UCP2 knockdown increased UCP4 expression, but not of UCP5. Our findings show that leptin preserves cell survival by maintaining MMP and ATP levels mediated through UCP2 in MPP+-induced toxicity.

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Alteration of mitochondrial oxidative capacity during porcine preadipocyte differentiation and in response to leptin

Cited by 25 publications

References 30 publications

Mild mitochondrial uncoupling does not affect mitochondrial biogenesis but downregulates pyruvate carboxylase in adipocytes: role for triglyceride content reduction

Mild mitochondrial uncoupling does not affect mitochondrial biogenesis but downregulates pyruvate carboxylase in adipocytes: role for triglyceride content reduction

Elevated skeletal muscle irisin precursor FNDC5 mRNA in obese OLETF rats

Mitochondrial Uncoupling Protein-2 (UCP2) Mediates Leptin Protection Against MPP+ Toxicity in Neuronal Cells

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