Expression of uncoupling protein‐3 and mitochondrial activity in the transition from hypothyroid to hyperthyroid state in rat skeletal muscle

Lanni, Antonia; Beneduce, Luca; Lombardi, Assunta; Moreno, María; Boss, Olivier; Muzzin, Patrick; Giacobino, Jean‐Paul; Goglia, Fernando

doi:10.1016/s0014-5793(99)00061-7

Cited by 113 publications

(84 citation statements)

References 38 publications

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“…Both UCP3 gene expression and state 4 mitochondrial respiration were also found to be lowest in skeletal muscle from patients with the least weight losses than in those with the greatest weight losses, following a hypocaloric slimming therapy [64]. The implications of these findings [62][63][64] are, however, questionable following the failure to confirm the observations of a link between UCP3 and state 4 respiration (and/or proton leak) in another UCP3-knockout mouse model [65,66].…”

Section: Ucp1-homologues: Are They Mediators Of Thermogenesis?mentioning

confidence: 99%

“…(iv) State 4 respiration controversies: It can always be argued that changes (or lack of it) in the gene or protein expression of UCP3 do not reflect changes in the activity of the protein. Indeed, the most direct evidence so far that UCP3 has physiologically relevant uncoupling properties rests à priori upon the report that state 4 respiration-which is often postulated to reflect basal proton leak respiration [62]-is lower in skeletal muscle from UCP3-knockout mice [63]. Both UCP3 gene expression and state 4 mitochondrial respiration were also found to be lowest in skeletal muscle from patients with the least weight losses than in those with the greatest weight losses, following a hypocaloric slimming therapy [64].…”

Section: Ucp1-homologues: Are They Mediators Of Thermogenesis?mentioning

confidence: 99%

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Adaptive thermogenesis and uncoupling proteins: a reappraisal of their roles in fat metabolism and energy balance

Dulloo

Seydoux

Jacquet

2004

Physiology & Behavior

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After decades of controversies about the quantitative importance of autoregulatory adjustments in energy expenditure in weight regulation, there is now increasing recognition that even subtle variations in thermogenesis could, in dynamic systems and over the long term, be important in determining weight maintenance in some and obesity in others. The main challenge nowadays is to provide a mechanistic explanation for the role of adaptive thermogenesis in attenuating and correcting deviations of body weight and body composition, and in the identification of molecular mechanisms that constitute its effector systems. This workshop paper reconsiders what constitutes adaptive changes in thermogenesis and reassesses the role of the sympathetic nervous system (SNS) and uncoupling proteins (UCP1, UCP2, UCP3, UCP5/BMCP1) as the efferent and effector components of the classical one-control system for adaptive thermogenesis and fat oxidation. It then reviews the evidence suggesting that there are in fact two distinct control systems for adaptive thermogenesis, the biological significance of which is to satisfy-in a lifestyle of famine-and-feast-the needs to suppress thermogenesis for energy conservation during weight loss and weight recovery even under environmental stresses (e.g., cold, infection, nutrient imbalance) when sympathetic activation of thermogenesis has equally important survival value.Keywords: Obesity; Diabetes; Cachexia; Catecholamines; UCP Resistance to obesity in an obesigenic environmentOne of the greatest challenges towards understanding the aetiology of human obesity is to explain how in environments that promote overeating of high-fat foods and discourage physical activity, there is always a section of the population who, apparently without conscious effort, do not become obese. How do they resist obesity? How is constancy of body weight achieved over decades in these individuals? In addressing the issue of human susceptibility to leanness and fatness, there are three cardinal features of body weight regulation that need to be underlined: (i) Humans cannot escape the laws of thermodynamics.Whatever theory is put forward to explain body weight and body composition regulation, it is undeniable that changes in body energy stores (and ultimately body weight) cannot occur unless there is a difference between energy intake and energy expenditure. (ii) Subtle perturbations in energy balance can lead to obesity. To put it another way, long-term constancy of body weight can only be achieved if the matching between energy intake and energy expenditure is extremely precise, since an error of only 1% between input and output of energy, if persistent, will lead to a gain or loss of 1 kg per year or some 40 kg between the age of 20 to 60 years. Yet, a difference of 5% between energy intake and energy expenditure is hardly measurable with available techniques. (iii) Body weight is a fluctuating and oscillatory phenomenon. Even in individuals that maintain a relatively stable lean body weight over decades, the...

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Section: Ucp1-homologues: Are They Mediators Of Thermogenesis?mentioning

confidence: 99%

Section: Ucp1-homologues: Are They Mediators Of Thermogenesis?mentioning

confidence: 99%

Adaptive thermogenesis and uncoupling proteins: a reappraisal of their roles in fat metabolism and energy balance

Dulloo

Seydoux

Jacquet

2004

Physiology & Behavior

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“…Because of their location, UCP2 and UCP3 may play important roles in the regulation of energy balance (11±14). Other important evidence pointing in this direction comes from reports that tri-iodothyronine (T 3 ) stimulates the expression of the mRNAs for UCP1 (15), UCP2 (16±19) and UCP3 (11,18,20,21). At least in the case UCP1, this stimulation seems to re¯ect a direct, not a permissive role (15).…”

Section: Introductionmentioning

confidence: 99%

Uncoupling protein 2 mRNA expression and respiratory parameters in Kupffer cells isolated from euthyroid and hyperthyroid rat livers

Voci

Demori²,

Franzi³

et al. 2001

Eur J Endocrinol

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Objective: The levels of uncoupling protein 2 (UCP2) mRNA and determinants of respiration (ATP synthesis, proton leak and non-mitochondrial respiration) were evaluated in Kupffer cells isolated from the livers of normal euthyroid, acute hyperthyroid and chronic hyperthyroid rats. Methods: After liver perfusion, Kupffer cells were puri®ed by density-gradient centrifugation followed by counter¯ow centrifugal elutriation. UCP2 mRNA levels were measured by Northern blot and respiratory parameters by polarographic method. Results: In cells isolated from hyperthyroid (tri-iodothyronine (T 3 )-treated) rats, the effect of T 3 treatment on the UCP2 mRNA level varied: it was more than doubled P , 0X05 in acutely T 3 -treated rats but, after chronic (3-week) T 3 treatment, it was only 30% (not statistically signi®cant) above the control (euthyroid) level. In Kupffer cells from the livers of chronic hyperthyroid rats, we observed an increase in total respiration rate, with an increase in the percentage attributable to the proton leak and a corresponding decrease in the percentage attributable to ATP synthesis (no alteration was observed in the percentage attributable to non-mitochondrial respiration). In the acute hyperthyroid rats, no signi®cant differences were observed in any of the respiratory parameters, although they all tended to increase. Conclusion: These data are indicative of a possible uncoupling effect of UCP2 in Kupffer cells. T 3 , by enhancing the expression of UCP2, could play a role in the energy homeostasis of these cells.

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“…Indeed, some studies have reported a correlation between UCP3 expression and increased oxygen consumption in skeletal muscle (5)(6)(7)(8). Several studies have shown that UCP3 mRNA in muscle, heart and adipose tissue is up-regulated by increased plasma free fatty acid levels due to starvation in humans (9,10), by a high lipid content diet (11) and by genetic/experimental diabetes in rodents (12).…”

mentioning

confidence: 99%

“…For instance, thyroid hormone (T 3 ) and hypercaloric/lipidic diets are known to be strong stimulators of UCP3 gene expression (5,7,8,16,17), yet it is not clear how such activators interact. Therefore, in the present study, the effect of T 3 and a hypercaloric diet on UCP3 gene expression in skeletal muscle was addressed by feeding rats a cafeteria diet.…”

mentioning

confidence: 99%

Hypercaloric cafeteria-like diet induced UCP3 gene expression in skeletal muscle is impaired by hypothyroidism

Christoffolete

Moriscot

2004

Braz J Med Biol Res

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The uncoupling protein UCP3 belongs to a family of mitochondrial carriers located in the inner mitochondrial membrane of certain cell types. It is expressed almost exclusively at high levels in skeletal muscle and its physiological role has not been fully determined in this tissue. In the present study we have addressed the possible interaction between a hypercaloric diet and thyroid hormone (T 3 ), which are strong stimulators of UCP3 gene expression in skeletal muscle. Male Wistar rats weighing 180 ± 20 g were rendered hypothyroid by thyroidectomy and the addition of methimazole (0.05%; w/v) to drinking water after surgery. The rats were fed a hypercaloric cafeteria diet (68% carbohydrates, 13% protein and 18% lipids) for 10 days and sacrificed by decapitation. Subsequently, the gastrocnemius muscle was dissected, total RNA was isolated with Trizol™ and UCP3 gene expression was determined by Northern blotting using a specific probe. Statistical analysis was performed by one-way analysis of variance (ANOVA) followed by the Student-Newman-Keuls posttest. Skeletal muscle UCP3 gene expression was decreased by 60% in hypothyroid rats and UCP3 mRNA expression was increased 70% in euthyroid cafeteria-fed rats compared to euthyroid chow-fed animals, confirming previous studies. Interestingly, the cafeteria diet was unable to stimulate UCP3 gene expression in hypothyroid animals (40% lower as compared to euthyroid cafeteria-fed animals). The results show that a hypercaloric diet is a strong stimulator of UCP3 gene expression in skeletal muscle and requires T 3 for an adequate action.

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Expression of uncoupling protein‐3 and mitochondrial activity in the transition from hypothyroid to hyperthyroid state in rat skeletal muscle

Cited by 113 publications

References 38 publications

Adaptive thermogenesis and uncoupling proteins: a reappraisal of their roles in fat metabolism and energy balance

Adaptive thermogenesis and uncoupling proteins: a reappraisal of their roles in fat metabolism and energy balance

Uncoupling protein 2 mRNA expression and respiratory parameters in Kupffer cells isolated from euthyroid and hyperthyroid rat livers

Hypercaloric cafeteria-like diet induced UCP3 gene expression in skeletal muscle is impaired by hypothyroidism

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