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

Abstract

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.

The Role and Regulatory Mechanism of Brown Adipose Tissue Activation in Diet-Induced Thermogenesis in Health and Diseases

“…Both cold-challenged and cafeteria-fed rats exhibited increases in circulating thyroid hormone levels [ 104 ]. In rats, overnutrition induced by a cafeteria diet is accompanied by a large increase in EE along with plasma T3 concentration [ 105 ]. T3 also acts as the main regulator of producing DIT in birds [ 106 ].…”

A Review of Brown Adipose Tissue Development in T2DM-SHR/N-cp (Corpulent) Rats

“…[1][2][3] As a result of the increased SNS activity in response to diet and environment, urinary excretion of norepinephrine metabolites via conversion to vanilmandelic acid becomes increased in proportion to the SNS activity and appears in the urine. 13,14 Glycosuria can contribute to an osmotic diuresis, resulting in increased volumes of urine especially in uncontrolled T2DM, while the osmotic impact of the urinary catecholamine metabolites is relatively minor in nature owing to the smaller osmolar contributions to final urine volumes. 14 The incidence of overweight and obese conditions has now become prevalent in numerous developed societies in concert with advances in nutritional science and technology, and where it now borders on becoming epidemic, in spite of numerous advances in nutrition knowledge and practice.…”

“…13,14 Glycosuria can contribute to an osmotic diuresis, resulting in increased volumes of urine especially in uncontrolled T2DM, while the osmotic impact of the urinary catecholamine metabolites is relatively minor in nature owing to the smaller osmolar contributions to final urine volumes. 14 The incidence of overweight and obese conditions has now become prevalent in numerous developed societies in concert with advances in nutritional science and technology, and where it now borders on becoming epidemic, in spite of numerous advances in nutrition knowledge and practice. 15 The overall impact on society of obesity and its related comorbidities including NIDDM, cardiovascular disease, and others has now placed an enormous burden on the economy due to lost productivity, and on the health care resources of developed societies.…”

Does clinical hypothyroidism occur in obesity? here is what the lab rats may be telling us about hope on the horizon

“…6,7 Parameters of energy expenditure have long been known to be heavily influenced via hormonal regulation, including parameters of sympathetic, thyroidal and Insulin actions. 8,9 Brown adipose tissue is a major organ for the expression of nonshivering thermogenesis in mammalian species, and dissections of the Interscapular brown fat depot, including determinations of IBAT mass and cellularity were consistently greater in the obese phenotype of several strains of genetically obese rats. 4,8 The increases in IBAT mass and cellularity in the cited studies were disproportionate to the diminished RMR and thermic responses to adrenergic stimulation observed among the obese rat strains.…”

“…8,9 Brown adipose tissue is a major organ for the expression of nonshivering thermogenesis in mammalian species, and dissections of the Interscapular brown fat depot, including determinations of IBAT mass and cellularity were consistently greater in the obese phenotype of several strains of genetically obese rats. 4,8 The increases in IBAT mass and cellularity in the cited studies were disproportionate to the diminished RMR and thermic responses to adrenergic stimulation observed among the obese rat strains. It is noteworthy that early overnutrition imposed via a highly palatable cafeteria diet to normally lean rats during postweaning growth (21 to 42 days postweaning) resulted in significant elevations in IBAT mass and cellularity, resting and norepinephrine stimulated thermogenesis, VMA and plasma T3.…”