Antidepressant Phenelzine Alters Differentiation of Cultured Human and Mouse Preadipocytes

F, Chiche; Guillou, Morwenna Le; Chétrite, G.; Lasnier, Françoise; Dugail, Isabelle; Carpéné, Christian; Moldes, Marthe; Fève, Bruno

doi:10.1124/mol.108.052563

Cited by 25 publications

(30 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whether the decrease in SSAO expression was a consequence of fat cell size reduction appears unlikely since the shrinking of lipid stores observed during prolonged fasting is not accompanied by a reduction of SSAO activity in adipose depots [28]. On the opposite, agents known to inhibit SSAO have been observed to limit lipogenesis in vitro [20]. On the basis of these previous observations, it can be proposed that inhibition of lipogenic effects of endogenous/dietary SSAO substrates participates to the limitation of fat deposition.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, benzylamine [17], methylamine [18], or other SSAO substrates [19], activate adipocyte differentiation in several preadipocyte lineages and therefore partly reproduce the adipogenic action of insulin. Lastly, in vitro experiments showed that the hydrazine derivative phenelzine (which inhibits SSAO) alters the adipocyte differentiation of cultured human and mouse preadipocytes [20]. We therefore hypothesized that endogenous or dietary amines may reproduce in vivo such anabolic insulin-like effects, and if the amines can reach WAT, any sustained pharmacological inhibition of their oxidation could hamper fat deposition.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Oral Administration of Semicarbazide Limits Weight Gain together with Inhibition of Fat Deposition and of Primary Amine Oxidase Activity in Adipose Tissue

Mercader

Iffiú-Soltész²,

Bour³

et al. 2011

Journal of Obesity

Self Cite

View full text Add to dashboard Cite

An enzyme hitherto named semicarbazide-sensitive amine oxidase (SSAO), involved in the oxidation of primary amines, is abundantly expressed in adipocytes. Although SSAO physiological functions remain unclear, several molecules inhibiting its activity have been described to limit fat accumulation in preadipocyte cultures or to reduce body weight gain in obese rodents. Here, we studied whether oral administration of semicarbazide, a prototypical SSAO inhibitor, limits fat deposition in mice. Prolonged treatment with semicarbazide at 0.125% in drinking water limited food and water consumption, hampered weight gain, and deeply impaired fat deposition. The adiposomatic index was reduced by 31%, while body mass was reduced by 15%. Such treatment completely inhibited SSAO, but did not alter MAO activity in white adipose tissue. Consequently, the insulin-like action of the SSAO substrate benzylamine on glucose transport was abolished in adipocytes from semicarbazide-drinking mice, while their insulin sensitivity was not altered. Although semicarbazide is currently considered as a food contaminant with deleterious effects, the SSAO inhibition it induces appears as a novel concept to modulate adipose tissue development, which is promising for antiobesity drug discovery.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oral Administration of Semicarbazide Limits Weight Gain together with Inhibition of Fat Deposition and of Primary Amine Oxidase Activity in Adipose Tissue

Mercader

Iffiú-Soltész²,

Bour³

et al. 2011

Journal of Obesity

Self Cite

View full text Add to dashboard Cite

show abstract

“…That may be a mechanism by which it causes weight gain. 115 The potent ability of PLZ to sequester toxic aldehydes may contribute to neuroprotective actions. 116 A PLZ metabolite produced by MAO has been proposed as the cause of GABA and alanine elevation 37 and increased brain ornithine, 117 but PLP deficiency may also be implicated.…”

Section: Differences Between Tcp and Phenelzinementioning

confidence: 99%

Advances Pertaining to the Pharmacology and Interactions of Irreversible Nonselective Monoamine Oxidase Inhibitors

Gillman¹

2011

Journal of Clinical Psychopharmacology

View full text Add to dashboard Cite

Recent advances clarifying the pharmacology and interactions of irreversible nonselective monoamine oxidase inhibitors that have not been considered in depth lately are discussed. These new data elucidate aspects of enzyme inhibition and pharmacokinetic interactions involving amine oxidases, cytochrome P450 enzymes, aminotransferases (transaminases), and decarboxylases (carboxy-lyases) and the effects of tyramine. Phenelzine and tranylcypromine remain widely available, and many publications have data relevant to this review. Their effect on CYP 450 enzymes is less than many newer drugs. Tranylcypromine only inhibits CYP 450 2A6 (selectively and potently). Phenelzine has no reported interactions, but, like isoniazid, weakly and irreversibly inhibits CYP 450 2C19 and 3A4 in vitro. It might possibly be implicated in interactions (as isoniazid is). Phenelzine has some clinically relevant inhibitory effects on amine oxidases, aminotransferases, and decarboxylases, and it lowers pyridoxal phosphate levels. It commonly causes pyridoxal deficiency, weight gain, sedation, and sexual dysfunction, but only rarely causes hepatic damage and failure, or neurotoxicity. The adverse effects and difficulties with monoamine oxidase inhibitors are less than previously believed or estimated, including a lower risk of hypertension, because the tyramine content in foods is now lower. Potent norepinephrine reuptake inhibitors have a strong protective effect against tyramine-induced hypertension. The newly discovered trace amine-associated receptors probably mediate the pressor response. The therapeutic potential of tranylcypromine and L-dopa in depression and Parkinson disease is worthy of reassessment. Monoamine oxidase inhibitors are not used to an extent proportionate with their benefits; medical texts and doctors' knowledge require a major update to reflect the evidence of recent advances.

show abstract

“…For T37i differentiation experiments, confluent cells were cultured in DMEM/Ham's F12, 10% FCS, 2 nM triiodothyronine (T3) and 20 nM insulin. Primary cultures of human subcutaneous preadipocytes were performed as previously described (Chiche et al, 2009). CBZ (Sigma Aldrich, Saint Quentin Fallavier, France) was dissolved in ethanol.…”

Section: Cell Culture and Differentiationmentioning

confidence: 99%

“…[ 3 H]-deoxyglucose ([ 3 H]-DOG) uptake and lipolysis were determined in mature adipocytes as previously mentioned (Chiche et al, 2009).…”

Section: Morphological and Biochemical Determinationsmentioning

confidence: 99%

Carbamazepine directly inhibits adipocyte differentiation through activation of the ERK 1/2 pathway

Turpin

Muscat

Vatier

et al. 2012

British J Pharmacology

View full text Add to dashboard Cite

BACKGROUND AND PURPOSECarbamazepine (CBZ), known for its anti-epileptic, analgesic and mood-stabilizing properties, is also known to induce weight gain but the pathophysiology of this adverse effect is still largely unknown. We tested the hypothesis that CBZ could have a direct effect on adipocyte development and metabolism. EXPERIMENTAL RESEARCHWe studied the effects of CBZ on morphological biochemical and molecular markers of adipogenesis, using several pre-adipocyte murine cell lines (3T3-L1, 3T3-F442A and T37i cells) and primary cultures of human pre-adipocytes. To delineate the mechanisms underlying the effect of CBZ, clonal expansion of pre-adipocytes, pro-adipogenic transcription factors, glucose uptake and lipolysis were also examined. KEY RESULTSCBZ strongly inhibited pre-adipocyte differentiation and triglyceride accumulation in a time-and dose-dependent manner in all models. Pleiotropic mechanisms were at the basis of the inhibitory effects of CBZ on adipogenesis and cell lipid accumulation. They included suppression of both clonal expansion and major adipogenic transcription factors such as PPAR-g and CCAAT/enhancer binding protein-a, activation of basal lipolysis and decrease in insulin-stimulated glucose transport. CONCLUSIONS AND IMPLICATIONSThe effect of CBZ on adipogenesis involves activation of the ERK1/2 pathway. Our results show that CBZ acts directly on pre-adipocytes and adipocytes to alter adipose tissue development and metabolism. AbbreviationsACC, acetyl-CoA carboxylase; C/EBP-a, CCAAT/enhancer binding protein-a; C/EBP-b, CCAAT/enhancer binding protein-b; CBZ, carbamazepine; DOG, deoxyglucose; FAS, fatty acid synthase; G3PDH, glycerol-3-phosphate dehydrogenase; HSL, hormone-sensitive lipase; MEK, MAPK/ERK kinase; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; SREBP-1c, sterol regulatory element-binding protein 1c

show abstract

Antidepressant Phenelzine Alters Differentiation of Cultured Human and Mouse Preadipocytes

Cited by 25 publications

References 40 publications

Oral Administration of Semicarbazide Limits Weight Gain together with Inhibition of Fat Deposition and of Primary Amine Oxidase Activity in Adipose Tissue

Oral Administration of Semicarbazide Limits Weight Gain together with Inhibition of Fat Deposition and of Primary Amine Oxidase Activity in Adipose Tissue

Advances Pertaining to the Pharmacology and Interactions of Irreversible Nonselective Monoamine Oxidase Inhibitors

Carbamazepine directly inhibits adipocyte differentiation through activation of the ERK 1/2 pathway

Contact Info

Product

Resources

About