Heat production during contraction in skeletal muscle of hypothyroid mice

Leijendekker, W. J.; Hardeveld, C. van; Elzinga, G.

doi:10.1152/ajpendo.1987.253.2.e214

Cited by 28 publications

(24 citation statements)

References 16 publications

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“…UCP3 activators FFAs and ROS accumulate in SKM during contraction or exercise (Watt et al, 2003;McArdle et al, 2004), and Curtin et al (2002) found that SKM UCP3 overexpression enhances the thermogenic response to contraction ex vivo, but no differences in muscle temperatures were apparent at rest. Likewise, for any given amount of mechanical work, EU SKM generates more heat than HYPO (Leijendekker et al, 1987). This increased thermogenesis probably results from activation of an UCP because compared with EU; SKM mitochondria from HYPER rats exhibit increased proton conductance (Brand et al, 1992) along with increased levels of ROS (Gredilla et al, 2001), FFAs (Lombardi et al, 2002), and coenzyme Q, a putative cofactor for UCP activity (Venditti et al, 2003).…”

Section: Determinants Of Sympathomimetic-induced Hyperthermia 277mentioning

confidence: 99%

Roles of Norepinephrine, Free Fatty Acids, Thyroid Status, and Skeletal Muscle Uncoupling Protein 3 Expression in Sympathomimetic-Induced Thermogenesis

Sprague

Yang

Sommers

et al. 2006

J Pharmacol Exp Ther

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Thyroid hormone (TH) plays a fundamental role in thermoregulation, yet the molecular mediators of its effects are not fully defined. Recently, skeletal muscle (SKM) uncoupling protein (UCP) 3 was shown to be an important mediator of the thermogenic effects of the widely abused sympathomimetic agents 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) and methamphetamine. Expression of UCP3 is regulated by TH. Activation of UCP3 is indirectly regulated by norepinephrine (NE) and is dependent upon the availability of free fatty acids (FFAs). We hypothesized that UCP3 may be a molecular link between TH and hyperthermia, requiring increased levels of both NE and FFAs to accomplish the thermogenic effect. Here, we demonstrate that MDMA (40 mg/kg s.c.) significantly increases plasma FFA levels 30 min after treatment. Pharmacologically increasing NE levels through the inhibition of phenylethanolamine N-methyltransferase with Ϯ2,3-dichloro-␣-methylbenzylamine potentiated the hyperthermic effects of a 20 mg/kg dose of MDMA. Using Western blots and regression analysis, we further illustrated that chronic hyperthyroidism in rats potentiates the hyperthermic effects of MDMA and increases levels of SKM UCP3 protein in a linear fashion according to levels of circulating plasma TH. Conversely, chronic hypothyroidism results in a hypothermic response to MDMA that is directly proportionate to decreased UCP3 expression. Acute TH supplementation did not change the skeletal muscle UCP3 expression levels or temperature responses to MDMA. These findings suggest that, although MDMA-induced hyperthermia appears to result from increased NE and FFA levels, susceptibility is ultimately determined by TH regulation of UCP3-dependent thermogenesis.Hyperthermia results from a severe, unregulated rise in core body temperature induced by high ambient temperature, strenuous exercise, endocrinopathy, or drug exposure. To our knowledge, no drug treatment has been established through controlled trials as an efficacious therapy for conditions that involve severe hyperthermia, with the exception of malignant hyperthermia, which is effectively reversed with dantrolene (Blank and Boggs, 1993). The lack of therapeutic options for the management of hyperthermia probably results from an inadequate understanding of the basic molecular mechanisms of thermogenesis.The principal active thyroid hormone (TH) 3,5,3Ј-triiodo-Lthyronine is formed from the precursor 3,5,3Ј,5Ј-tetraiodothyronine (T 4 , thyroxine) by deiodinases present in various tissues (Bianco and Larsen, 2005). Although TH has been established as the primary endocrinologic regulator of body temperature (Silva, 2005) and facultative thermogenesis (FT) (for review see Lowell and Spiegelman, 2000), the mechanisms involved are complex and incompletely characterized. One family of genes regulated by TH (Gong et al., 1997) and believed to play a significant role in FT encodes for the mitochondrial uncoupling proteins (UCPs).UCPs "uncouple" free energy stored in the mitochondrial electrochemical p...

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Section: Determinants Of Sympathomimetic-induced Hyperthermia 277mentioning

confidence: 99%

Roles of Norepinephrine, Free Fatty Acids, Thyroid Status, and Skeletal Muscle Uncoupling Protein 3 Expression in Sympathomimetic-Induced Thermogenesis

Sprague

Yang

Sommers

et al. 2006

J Pharmacol Exp Ther

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“…At the end of experiments, the length of fibre bundles was measured, tendons were removed and muscles were dried for at least 24 h. Dry weight was measured using an electronic balance (Cahn 25, Cahn Instruments, Cerritos, CA, USA). To allow comparison with previous results, wet weight was estimated assuming a wet/dry weight ratio of 5*0 (Leijendekker, Hardeveld & Elzinga, 1987).…”

Section: Experimental Protocolsmentioning

confidence: 99%

Energetics of fast‐ and slow‐twitch muscles of the mouse.

Barclay

Constable

Gibbs

1993

The Journal of Physiology

184

194

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SUMMARY1. The energetic cost of work performance by mouse fast-and slow-twitch muscle was assessed by measuring the rates of thermal and mechanical energy liberation of the muscles at 21 'C. Thermal energy (heat) liberation was measured using a fastresponding thermopile.2. Bundles of muscle fibres from the slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles were used. Work output was controlled by performing isovelocity shortenings during the plateau of an isometric tetanus. A range of shortening velocities, spanning the possible range, was used for each muscle.3. During tetanic contractions, the rate of heat production from EDL muscle was 134-2 + 11-4 mW/g. The rate of heat production by soleus muscle was only one-fifth as great (26-8 + 2-7 mW/g).4. The maximum shortening velocity (Vmax) of EDL muscles was 2*5-fold greater than that for soleus muscles and it's force-velocity relationship was less curved. Peak power output from EDL muscles was 3-fold greater than that from soleus muscle.5. During shortening, the rate of heat output from soleus muscles increased considerably above the isometric heat rate. In contrast to soleus muscle, the rate of heat production by EDL muscle increased by only a small fraction of the isometric heat rate. The magnitude of the increases in rate was proportional to shortening velocity.6. The total rate of energy liberation (heat rate + power) by EDL muscle, shortening at 0 95 Vmax was 1-62 + 0 37 times greater than the isometric heat rate. In contrast, the rate of energy liberation from soleus muscle shortening at 0 95 Vmax was 5-21 + 0-58 times greater than its isometric heat rate. The peak mechanical efficiency (power/total energy rate) of the both muscles was approximately 30%.

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“…Not only TH increases the number of energy transformations, as evidenced by 30À50% reduced minimal energy cost of living and reflected by BMR or resting energy expenditure (REE) in hypothyroidism, but it also reduces the thermodynamic efficiency of the homeothermic machine for the sake of producing more heat. For example, for any amount of mechanical work, euthyroid rat muscles generate more heat than the hypothyroid counterpart (Leijendekker et al, 1987). Likewise, the energy cost of producing a given amount of glycogen from lactate is higher in euthyroid than hypothyroid hepatocytes (Berry et al, 1989).…”

Section: Thyroid Hormone (Th) Thermogenesis and Temperature Homeostasismentioning

confidence: 99%

Thyroid Hormone and the Energetic Cost of Keeping Body Temperature

Silva

2005

Bioscience Reports

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By definition, homeothermic species maintain their core temperature (T c ) regulated within narrow limits. In most of these species, the hypothalamic thermostat is set somewhere between 36 and 38°C, and T c is tightly kept there, in spite of highly variable ambient temperatures. Several mechanisms to maintain body temperature have been selected during evolution. Vasoconstriction and piloerection are mechanisms to save heat, while vasodilatation, sweating and perspiration are mechanisms to rapidly dissipate heat. To maintain temperature in environments usually colder than T c , homeothermic species need to produce more heat than poikilothermic species. Energy transformations generate heat simply by virtue of the laws of thermodynamics and so the energy transformations inherent to life generate heat. Such heat, generated as byproduct of cell vital functions, is called obligatory thermogenesis (OT) and is expectedly higher in homeothermic species, as a consequence of which metabolic rate is substantially higher in these species than in poikilothermic species (Else and Hulbert, 1981). In addition to having a higher OT, homeothermic species can also activate specific mechanisms to produce extra heat in cold environments, which is called facultative thermogenesis (Gordon, 1993). Muscle shivering is the most immediate form of facultative thermogenesis, but it is energy consuming and disruptive for activity, and is rapidly replaced by metabolic heat production or non-shivering facultative thermogenesis (for simplicity we will call the former ''shivering'' and the latter ''facultative thermogenesis'', FT). There is an ambient temperature range, called thermoneutral zone, where OT is sufficient per se to maintain body temperature, without the need of FT or heat saving or heat dissipating mechanisms (Gordon, 1993). Such ambient temperature zone is quite narrow, but empirically it is possible to define a lower and an upper boundary (Gordon, 1993). In this discussion, I will talk rather of thermoneutrality temperature, T N , which corresponds to the low end of the thermoneutral zone and is defined as the minimal ambient temperature where OT can alone maintain body temperature.

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Heat production during contraction in skeletal muscle of hypothyroid mice

Cited by 28 publications

References 16 publications

Roles of Norepinephrine, Free Fatty Acids, Thyroid Status, and Skeletal Muscle Uncoupling Protein 3 Expression in Sympathomimetic-Induced Thermogenesis

Roles of Norepinephrine, Free Fatty Acids, Thyroid Status, and Skeletal Muscle Uncoupling Protein 3 Expression in Sympathomimetic-Induced Thermogenesis

Energetics of fast‐ and slow‐twitch muscles of the mouse.

Thyroid Hormone and the Energetic Cost of Keeping Body Temperature

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