Nitric oxide dysregulates adipocytokine expression in 3T3-L1 adipocytes

Nozaki, Maiko; Fukuhara, Atsunori; Segawa, Katsumori; Okuno, Yosuke; Abe, Manabu; Hosogai, Naomi; Matsuda, Morihiro; Komuro, Ryutaro; Shimomura, Iichiro

doi:10.1016/j.bbrc.2007.09.084

Cited by 27 publications

(19 citation statements)

References 35 publications

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“…Our present results demonstrate that NO is an important mediator in the long-term leptin-induced downregulation of lipolysis, glyceroneogenesis, the key genes in these pathways, and their major transcriptional regulator, PPARg. Such results are in agreement with other studies carried out on 3T3-L1 adipocytes or with iNOS2/2 transgenic mice that concluded that NO reduced PPARg expression in adipocytes (36,37).…”

Section: Discussionsupporting

confidence: 95%

Leptin Induces Nitric Oxide-Mediated Inhibition of Lipolysis and Glyceroneogenesis in Rat White Adipose Tissue

Niang

Benelli

Ribière

et al. 2011

The Journal of Nutrition

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Leptin is secreted by white adipose tissue (WAT) and induces lipolysis and nonesterified fatty acid (NEFA) oxidation. During lipolysis, NEFA efflux is the result of triglyceride breakdown, NEFA oxidation, and re-esterification via glyceroneogenesis. Leptin's effects on glyceroneogenesis remain unexplored. We investigated the effect of a long-term treatment with leptin at a physiological concentration (10 μg/L) on lipolysis and glyceroneogenesis in WAT explants and analyzed the underlying mechanisms. Exposure of rat WAT explants to leptin for 2 h resulted in increased NEFA and glycerol efflux. However, a longer treatment with leptin (18 h) did not affect NEFA release and reduced glycerol output. RT-qPCR showed that leptin significantly downregulated the hormone-sensitive lipase (HSL), cytosolic phosphoenolpyruvate carboxykinase (Pck1), and PPARγ genes. In agreement with its effect on mRNA, leptin also decreased the levels of PEPCK-C and HSL proteins. Glyceroneogenesis, monitored by [1-(14) C] pyruvate incorporation into lipids, was reduced. Because leptin increases nitric oxide (NO) production in adipocytes, we explored the role of NO in the leptin signaling pathway. Pretreatment of explants with the NO synthase inhibitor Nω-nitro-l-arginine methyl ester eliminated the effect of leptin on lipolysis, glyceroneogenesis, and expression of the HSL, Pck1, and PPARγ genes. The NO donor S-nitroso-N-acetyl-DL penicillamine mimicked leptin effects, thus demonstrating the role of NO in these pathways. The inverse time-dependent action of leptin on WAT is consistent with a process that limits NEFA re-esterification and energy storage while reducing glycerol release, thus preventing hypertriglyceridemia.

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Section: Discussionsupporting

confidence: 95%

Leptin Induces Nitric Oxide-Mediated Inhibition of Lipolysis and Glyceroneogenesis in Rat White Adipose Tissue

Niang

Benelli

Ribière

et al. 2011

The Journal of Nutrition

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“…NO downregulates adiponectin synthesis in adipose tissue [11] while a chronic blockade of NO synthesis reduces adiposity and improves insulin resistance in mice [12]. However, other results suggested a positive relationship between NO and adiponectin [13].…”

Section: Introductionmentioning

confidence: 58%

“…The age of obese children (n = 79) was 13.33 ± 0.34 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) years, not significantly different from the healthy controls (n = 12, 11.63 ± 1.61, 8-19 years). Obese children were divided into subgroups according to their age (5-10 years, n = 16; 11-14 years, n = 29; 15-17 years, n = 34), to gender (males, n = 44/females, n = 35) and NOS positivity (n = 17)/negativity (n = 62) of their isolated white blood cells (WBC-NOS II).…”

Section: Patientsmentioning

confidence: 99%

Role of nitric oxide (NO) metabolism and inflammatory mediators in childhood obesity

et al. 2011

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“…iNOS-knockout mice have been reported to be protected from high-fat diet-induced IR [41]. Additionally, iNOS-induced NO in serum decreased the production of insulin-sensitive adipokines, adiponectin, and leptin from adipocytes [42] and increased the insulin-resistant factors PAI-1 and interleukin-6 [43]. Agents that modulate the bioactivity of endogenously-produced NO have therefore received much attention as potential therapeutic agents.…”

Section: Sex Hormones Affect the No/ Inducible No Sythase Pathwaymentioning

confidence: 99%

Sex hormones influence expression and function of peroxisome proliferator-activated receptor γ in adipocytes: pathophysiological aspects

Sato

Ishikawa

Sugai

et al. 2014

Hormone Molecular Biology and Clinical Investigation

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Adipose tissue plays important roles not only in storing fat but also in maintaining metabolic homeostasis by regulating hundreds of biological signaling events and the secretion of various cytokines. One of the central regulators of adipocyte differentiation is peroxisome proliferator-activated receptor γ (PPARγ), which promotes downstream transcriptional activities, such as adiponectin. Disruption of homeostasis leads to the onset of metabolic diseases such as type 2 diabetes and other triggers for metabolic syndrome. Males and post-menopausal females are more likely to be affected with metabolic diseases than pre-menopausal females, suggesting that sex hormones might be involved in the pathogenesis and development of metabolic diseases. Indeed, 17β-estradiol, testosterone, dihydrotestosterone, and their receptors clearly play a role in adipose regulation: they can alter fat distribution and can modify the expression and activities of PPARγ and its downstream adipocytokines. Furthermore, sex hormones affect inflammatory factors such as nitric oxygen, nitric oxygen synthase, and their surrounding components. Sex hormones are also suggested to be involved with sex differences in the efficacy of the PPARγ agonist thiazolidinediones. Therefore, thorough investigation of how sex hormone-dependent regulation of metabolic homeostasis occurs is necessary in order to develop individualized clinical therapies optimized with regard to each patient's biological condition and drug sensitivities.

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Nitric oxide dysregulates adipocytokine expression in 3T3-L1 adipocytes

Cited by 27 publications

References 35 publications

Leptin Induces Nitric Oxide-Mediated Inhibition of Lipolysis and Glyceroneogenesis in Rat White Adipose Tissue

Leptin Induces Nitric Oxide-Mediated Inhibition of Lipolysis and Glyceroneogenesis in Rat White Adipose Tissue

Role of nitric oxide (NO) metabolism and inflammatory mediators in childhood obesity

Sex hormones influence expression and function of peroxisome proliferator-activated receptor γ in adipocytes: pathophysiological aspects

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