Failure of α-Methyltyrosine to Inhibit Peripheral Triiodothyronine Formation*

Dvorak, J.; Engelman, Karl; Utiger, Robert D.

doi:10.1210/jcem-47-2-442

Cited by 3 publications

(2 citation statements)

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“…Measure of circulating T3 were determined by solid phase radioimmunoassay and data were analyzed by paired t-test and student Neuman-Keuls subgroup analysis via standard statistical procedures. Measures of VO2 were determined under thermal neutral conditions (30°C) established for rodents, corrected to surface area as described by Kleiber and Wang et al 22 with a Collins small animal respirometer apparatus and plexiglass small animal chamber specially modified to enable strict temperature control. 23 The measures of thermogenesis were further corrected to account for potential α-MPT induced differences in body temperature due to decreases in SNS activity at the time of measurement.…”

Section: Methodsmentioning

confidence: 99%

Sympathetic blockade on diet induced thermogenesis in the congenic LA/Ntul//-cp rat

Tulp¹

2022

EMIJ

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The effects of overfeeding highly palatable diets via the cafeteria feeding diet method (Café) has been shown to be a reliable experimental model to induce diet induced thermogenesis (DIT) in young adult normally lean rats of several strains. Groups of young adult lean LA/ Ntul//-cp rats were offered a Purina chow diet (CHOW) or the same diet plus a daily café supplement both ad libitum from 10 until 24 weeks of age. The drug α-methylparatyrosine (α-MPT) was administered to groups (250 mg α-MPT/kg BW, i.p.) to ablate sympathetic (SNS) activity or a sham injection of physiologic saline given, and measures of fasting resting thermogenesis obtained at thermal neutrality (30°C) before and after the α-MPT or sham administration. The Café diet resulted in a 67% increase in body weight (BW) and a ~25% increase in resting oxygen consumption (VO2) following café overfeeding in both groups, while only a 40% increase in BW and no additional increase in VO2 occurred in normally CHOW fed rats while the sham injection was without any variations from normal physiologic responses as predicted. Sympathetic blockade with α-MPT was associated with modest decreases in body temperature and an average ~12-15% decrease in VO2 in the café treated group, but when the VO2 data were arithmetically corrected to isothermal conditions only a net 3% decrease occurred in CHOW fed rats and was without effect on the SHAM group. Serum T3 concentrations increased by 92% and urinary catecholamine excretion of VMA >250% following the café diet, but the urinary vanilmandelic acid (VMA) excretion was virtually nil following the sympathetic blockade. These observations indicate that the SNS-mediated contribution component to DIT following prolonged café overfeeding under conditions of thermal neutrality contribute approximately 50% of the thermic response. While under normal long term CHOW feeding the SNS component may be as little as 3% of the thermic response, and thus, the total thermic response of DIT likely represents a combination of short acting SNS and longer acting non-SNS mechanisms, including a likely significant thyroidal component in normally lean animals.

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Section: Methodsmentioning

confidence: 99%

Sympathetic blockade on diet induced thermogenesis in the congenic LA/Ntul//-cp rat

Tulp¹

2022

EMIJ

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“…Thus, the use of α-MPT is well suited for the qualitative separation of the SNS and thyroidal components 0f DIT and NST, especially since it has long to been known to be without any effects on iodothyronine metabolism in rats or humans, in contrast to insulin and nutritional factors, both of which are linked to iodothyronine deiodination. [16][17][18][19] Thus, the purpose of the present study was to determine the relative contributions of the SNS and non-SNS components of NST in lean rats fed a low glycemic chow diet or chronically overfed with a Café diet feeding regimen.…”

Section: Introductionmentioning

confidence: 99%

Treatment with α-Methylparatyrosine Inhibits Sympathetic but Not Thyroidal Responses to Diet-Induced Thermogenesis in Lean Cafeteria-Overfed Rats

Tulp¹

2022

CTTPR

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The sympathoplegic drug α-methylparatyrosine (α-MPT) was administered to lean, normally fed rats or rats overfed to induce diet induced thermogenesis (DIT) with a highly palatable Cafeteria diet regimen (Café) for twelve weeks, and measures of resting thermogenesis under thermoneutral conditions (VO2 at ambient 30°C), serum T3 and 24-hour urinary vanilmandelic acid (VMA) excretion determined before and after the α-MPT treatment. The café diet resulted in significant increases in VO2, serum T3, and VMA excretion. The α-MPT resulted in approximately fifty percent decrease in the Café-induced increase in VO2 after 24hours, while thyroidal function appeared clinically unaffected. These observations suggest that the sympathetic contributions to diet-induced thermogenesis (DIT) following chronic overfeeding with the Café diet regimen represent only about half of the reported dietary induced thermic response to overfeeding and non-sympathetic contributions including the thyroidal actions that likely account for the remaining proportion of the increased DIT and sympathetic component may decrease further over time spent since feeding.

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Sympathetic blockade on diet induced thermogenesis in the congenic LA/Ntul//-cp rat

L Tulp

2023

EMIJ

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The effects of overfeeding highly palatable diets via the cafeteria feeding diet method (Café) has been shown to be a reliable experimental model to induce diet induced thermogenesis (DIT) in young adult normally lean rats of several strains. Groups of young adult lean LA/Ntul//-cp rats were offered a Purina chow diet (CHOW) or the same diet plus a daily café supplement both ad libitum from 10 until 24 weeks of age. The drug α-methylparatyrosine (α-MPT) was administered to groups (250 mg α-MPT/kg BW, i.p.) to ablate sympathetic (SNS) activity or a sham injection of physiologic saline given, and measures of fasting resting thermogenesis obtained at thermal neutrality (30°C) before and after the α-MPT or sham administration. The Café diet resulted in a 67% increase in body weight (BW) and a ~25% increase in resting oxygen consumption (VO2) following café overfeeding in both groups, while only a 40% increase in BW and no additional increase in VO2 occurred in normally CHOW fed rats while the sham injection was without any variations from normal physiologic responses as predicted. Sympathetic blockade with α-MPT was associated with modest decreases in body temperature and an average ~12-15% decrease in VO2 in the café treated group, but when the VO2 data were arithmetically corrected to isothermal conditions only a net 3% decrease occurred in CHOW fed rats and was without effect on the SHAM group. Serum T3 concentrations increased by 92% and urinary catecholamine excretion of VMA >250% following the café diet, but the urinary vanilmandelic acid (VMA) excretion was virtually nil following the sympathetic blockade. These observations indicate that the SNS-mediated contribution component to DIT following prolonged café overfeeding under conditions of thermal neutrality contribute approximately 50% of the thermic response. while under normal long term CHOW feeding the SNS component may be as little as 3 % of the thermic response, and thus, the total thermic response of DIT likely represents a combination of short acting SNS and longer acting non-SNS mechanisms, including a likely significant thyroidal component in normally lean animals.

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Failure of α-Methyltyrosine to Inhibit Peripheral Triiodothyronine Formation*

Cited by 3 publications

References 0 publications

Sympathetic blockade on diet induced thermogenesis in the congenic LA/Ntul//-cp rat

Sympathetic blockade on diet induced thermogenesis in the congenic LA/Ntul//-cp rat

Treatment with α-Methylparatyrosine Inhibits Sympathetic but Not Thyroidal Responses to Diet-Induced Thermogenesis in Lean Cafeteria-Overfed Rats

Sympathetic blockade on diet induced thermogenesis in the congenic LA/Ntul//-cp rat

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