Thermogenic Mechanisms and their Control

Himms‐Hagen, Jean; Cerf, Jean; Desautels, M.; Zaror-Behrens, Gloria

doi:10.1007/978-3-0348-5559-4_14

Cited by 22 publications

(19 citation statements)

References 38 publications

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“…Sympathomimetic agents such as MDMA and methamphetamine increase body temperature by preventing heat dissipation via α 1 -mediated peripheral vasoconstriction (27) and by generating heat through the activation of mitochondrial uncoupling proteins (UCP3; 28). Adrenergic activation by these agents results in peripheral norepinephrine release and subsequent activation of α 1 - and β 3 -adrengergic receptors (AR) (29,30,31). β 3 -AR activation leads to cAMP-mediated stimulation of hormone sensitive lipase (HSL) and subsequent release of free fatty acids (FFA).…”

Section: Discussionmentioning

confidence: 99%

Synthetic Cathinones (“Bath Salts”)

Banks

Worst

Rusyniak

et al. 2014

The Journal of Emergency Medicine

141

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Background Synthetic cathinones are popularly referred to in the media as “bath salts.” Through the direct and indirect activation of the sympathetic nervous system, smoking, snorting, or injecting synthetic cathinones can result in tachycardia, hypertension, hyperthermia, myocardial infarction and death. Objectives The chemical structures and names of bath salts identified by the State of Ohio Bureau of Criminal Identification and Investigation Laboratory are presented. Based on their common pharmacophores the authors review the history, pharmacology, toxicology, detection methods and clinical implications of synthetic cathinones. Through the integration of this information, the pharmacological basis for the management of patients using synthetic cathinones is presented. Discussion Synthetic cathinones activate central serotonergic and dopaminergic systems contributing to acute psychosis and the peripheral activation of the sympathetic nervous system. The over stimulation of the sympathetic nervous system contributes to the many toxicities reported with bath salt use. The pharmacological basis for managing these patients is targeted at attenuating the activation of these systems. Conclusions Treatment of patients presenting after using bath salts should be focused on reducing agitation and psychosis, and supporting renal perfusion. The majority of successfully treated synthetic cathinones cases have used benzodiazepines and antipsychotics along with general supportive care.

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Section: Discussionmentioning

confidence: 99%

Synthetic Cathinones (“Bath Salts”)

Banks

Worst

Rusyniak

et al. 2014

The Journal of Emergency Medicine

141

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“…Sympathetic nervous system activation by MDMA results in peripheral norepinephrine release and subsequent activation of α 1 - and β 3 -adrenergic receptors (Kuusela et al, 1997; Zhao et al, 1997; Himms-Hagen et al, 1978). β 3 -adrenergic receptor activation leads to cAMP-mediated stimulation of hormone sensitive lipase and subsequent release of free fatty acids (FFA).…”

Section: Introductionmentioning

confidence: 99%

Pharmacodynamic characterization of insulin on MDMA-induced thermogenesis

Banks

Buzard

Gehret

et al. 2009

European Journal of Pharmacology

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Sympathomimetic drugs (MDMA; Ecstasy) induce a potentially catastrophic hyperthermia that involves free fatty acid (FFA) activation of mitochondrial uncoupling proteins (UCP). Insulin is an important regulator of plasma FFA levels, although its role in thermogenesis is unclear. The aims of the present study were 1) to characterize the pharmacodynamic effects of MDMA on plasma insulin and glucose, 2) to examine the effects of insulin on MDMA-induced thermogenesis and 3) to examine MDMA-induced thermogenesis in an animal model of insulin resistance, the obese Zucker rat. Insulin levels peaked 15 min. after MDMA (40 mg/kg, sc), which preceded the peak temperature change at 60 min. Plasma glucose levels also peaked 15 min. after MDMA and remained elevated throughout the 90-min. monitoring period. Insulin pretreatment (10 units/kg, sc) 30 min. before a low dose of MDMA (5 mg/kg, sc) potentiated the thermogenic response. Insulin resistant, fa/fa (obese) Zucker rats demonstrated an attenuated thermogenic response to MDMA (40 mg/kg, sc). Consistent with the role for FFA in UCP3 expression, immunoblot analysis showed significantly increased levels of UCP3 protein in obese compared to lean Zucker skeletal muscle. In conclusion, the results of the present study suggest a potential role of insulin signaling in sympathomimetic-induced thermogenesis.

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“…In adult obese animals, the amount of thermogenically active BAT as well as the expression of ␤ 3 -adrenoceptors in brown adipocytes are substantially reduced, potentially resulting in alterations of metabolic function and thermoregulation (3)(4)(5). The molecular basis of these obesity-related changes is poorly understood.…”

mentioning

confidence: 99%

Tumor necrosis factor α mediates apoptosis of brown adipocytes and defective brown adipocyte function in obesity

Nisoli

Briscini

Giordano

et al. 2000

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

122

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Severe quantitative and qualitative brown adipocyte defects are common in obesity. To investigate whether aberrant expression of tumor necrosis factor ␣ (TNF-␣) in obesity is involved in functional brown fat atrophy, we have studied genetically obese (ob͞ob) mice with targeted null mutations in the genes encoding the two TNF receptors. The absence of both TNF receptors or p55 receptor alone resulted in a significant reduction in brown adipocyte apoptosis and an increase in ␤3-adrenoreceptor and uncoupling protein-1 expression in obese mice. Increased numbers of multilocular functionally active brown adipocytes, and improved thermoregulation was also observed in obese animals lacking TNF-␣ function. These results indicate that TNF-␣ plays an important role in multiple aspects of brown adipose tissue biology and mediates the abnormalities that occur at this site in obesity. O besity in experimental models is ubiquitously associated with abnormalities in brown adipose tissue (BAT) (1, 2). In adult obese animals, the amount of thermogenically active BAT as well as the expression of ␤ 3 -adrenoceptors in brown adipocytes are substantially reduced, potentially resulting in alterations of metabolic function and thermoregulation (3-5). The molecular basis of these obesity-related changes is poorly understood. It has been demonstrated that expression of tumor necrosis factor ␣ (TNF-␣) in adipose tissue is elevated in a variety of experimental obesity models (6-9) and obese humans (10, 11). Owing to its ability to inhibit insulin receptor signaling (12-14), TNF-␣ represents a component of obesity-related insulin resistance (15). More recently, TNF-␣ has been shown to induce brown and white adipocyte apoptosis in vitro (16)(17)(18). Interestingly, in genetic models of obesity, the number of apoptotic cells in the brown fat is dramatically higher than that in control animals (16). This leads to reduction in the number of multilocular thermogenically active brown fat cells and therefore causes BAT functional atrophy, which is characterized by defective thermoregulation in both genetic and dietary obesity. In addition, because BAT is an important target for insulin action and other aspects of energy metabolism, its atrophy could further contribute to the abnormal metabolic profile in obesity. Here, we have tested whether abnormal TNF-␣ production in obesity contributes to any of these abnormalities in BAT. Materials and MethodsGeneration of ob͞ob Mice Deficient in TNF Receptors (TNFR). Obese (ob͞ob) mice deficient in TNFR were generated as described (19)(20)(21). Mice with targeted null mutations at both TNFR 1 and 2 loci (p55, respectively) were crossed with Ob͞ob mice, to produce animals heterozygous at the TNFR1, TNFR2, and ob loci (p55, and Ob͞ob). The resulting triple heterozygotes were then crossbred with each other to produce OB͞ob mice wild type at TNFR loci or with homozygous null mutations in each or both TNFR. The subsequent intercrossing of these animals produced control OB͞OB and ob͞ob mice and littermates with m...

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Thermogenic Mechanisms and their Control

Cited by 22 publications

References 38 publications

Synthetic Cathinones (“Bath Salts”)

Synthetic Cathinones (“Bath Salts”)

Pharmacodynamic characterization of insulin on MDMA-induced thermogenesis

Tumor necrosis factor α mediates apoptosis of brown adipocytes and defective brown adipocyte function in obesity

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