Brown fat thermogenesis in cold-acclimated rats is not abolished by the suppression of thyroid function

Zaninovich, Angel A.; Raı́ces, Marcela; Rebagliati, Inés; Ricci, C.; Hagmüller, K.

doi:10.1152/ajpendo.00540.2001

Cited by 27 publications

(25 citation statements)

References 42 publications

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“…2 and Figs. S1 and S2) and strongly suggest the detected bands correspond to different UCP1 species, which are known to migrate on immunoblot at slightly different levels in different preparations and tissues, possibly as a result of posttranslational modifications (31)(32)(33)(34)(35). Notably, compared with tissues from summer active squirrels, we detected significant upregulation of UCP1 protein in mitochondrial lysates from torpid brain, cortex, and spinal cord (P = 0.0194, P = 0.0158, and P = 0.016, respectively; unpaired t test; n ≥ 3 experiments) (Fig.…”

Section: Resultsmentioning

confidence: 82%

Neuronal UCP1 expression suggests a mechanism for local thermogenesis during hibernation

Laursen

Mastrotto

Pesta

et al. 2015

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

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Hibernating mammals possess a unique ability to reduce their body temperature to ambient levels, which can be as low as −2.9°C, by active down-regulation of metabolism. Despite such a depressed physiologic phenotype, hibernators still maintain activity in their nervous systems, as evidenced by their continued sensitivity to auditory, tactile, and thermal stimulation. The molecular mechanisms that underlie this adaptation remain unknown. We report, using differential transcriptomics alongside immunohistologic and biochemical analyses, that neurons from thirteen-lined ground squirrels (Ictidomys tridecemlineatus) express mitochondrial uncoupling protein 1 (UCP1). The expression changes seasonally, with higher expression during hibernation compared with the summer active state. Functional and pharmacologic analyses show that squirrel UCP1 acts as the typical thermogenic protein in vitro. Accordingly, we found that mitochondria isolated from torpid squirrel brain show a high level of palmitate-induced uncoupling. Furthermore, torpid squirrels during the hibernation season keep their brain temperature significantly elevated above ambient temperature and that of the rest of the body, including brown adipose tissue. Together, our findings suggest that UCP1 contributes to local thermogenesis in the squirrel brain, and thus supports nervous tissue function at low body temperature during hibernation.T hirteen-lined ground squirrels (Ictidomys tridecemlineatus) are obligatory hibernating mammals. They are found across a wide range of latitudes, from southern Canada to the Gulf of Mexico. In northern habitats with long winters and limited food resources, ground squirrels breed only once a year, in late spring, and then hibernate in underground burrows from October to April. Hibernation consists of cycling between bouts of torpor and brief interbout arousal periods, each usually lasting less than 24 h (1, 2).During the long hibernation season, torpid animals undergo dramatic perturbations, including reduction in heart, respiratory, and overall metabolic rates, as well as decreases in core body temperature from 37°C to just above ambient temperature (often as low as 1-5°C) (2). Despite such a depressed physiologic phenotype, torpid animals remain sensitive to their environment (3). For example, during extreme winters, when ambient burrow temperatures reach the freezing point of water, most hibernating mammals increase metabolic activity and warm up as a safety precaution to prevent freezing (4). Similarly, arousal can be triggered by sound, touch, or a sudden increase in ambient temperature (3, 5). Thus, hibernating animals maintain activity in their peripheral and central nervous systems. Indeed, physiologic experiments conducted on nerve fibers isolated from torpid hamsters and squirrels demonstrated the ability to generate action potentials at temperatures prohibitively low for their nonhibernating relatives (i.e., rats, mice) (6-8).Deeply hibernating animals can keep their brain temperatures elevated above ambient by seve...

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Section: Resultsmentioning

confidence: 82%

Neuronal UCP1 expression suggests a mechanism for local thermogenesis during hibernation

Laursen

Mastrotto

Pesta

et al. 2015

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

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“…Our findings of increased BAT weight and cell hypertrophy in cold-exposed POMC-Ptp1b Ϫ/Ϫ compared with Ptp1b ϩ/ϩ mice suggest altered thermogenic capacity of BAT in POMCPtp1b Ϫ/Ϫ mice. It is clear the BAT undergoes hypertrophy in response to cold (16,61), which signifies increased thermo- genesis. It is also likely that intact hypothalamic LepR signaling is required for maintaining cold tolerance (30).…”

Section: Pomc-ptp1bmentioning

confidence: 99%

Deficiency of PTP1B in POMC neurons leads to alterations in energy balance and homeostatic response to cold exposure

Jonghe¹,

Hayes

Banno³

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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EA, Grill HJ, Bence KK. Deficiency of PTP1B in POMC neurons leads to alterations in energy balance and homeostatic response to cold exposure. Am J Physiol Endocrinol Metab 300: E1002-E1011, 2011. First published March 15, 2011; doi:10.1152/ajpendo.00639.2010.-The adipose tissue-derived hormone leptin regulates energy balance through catabolic effects on central circuits, including proopiomelanocortin (POMC) neurons. Leptin activation of POMC neurons increases thermogenesis and locomotor activity. Protein tyrosine phosphatase 1B (PTP1B) is an important negative regulator of leptin signaling. POMC neuron-specific deletion of PTP1B in mice results in reduced high-fat diet-induced body weight and adiposity gain due to increased energy expenditure and greater leptin sensitivity. Mice lacking the leptin gene (ob/ob mice) are hypothermic and cold intolerant, whereas leptin delivery to ob/ob mice induces thermogenesis via increased sympathetic activity to brown adipose tissue (BAT). Here, we examined whether POMC PTP1B mediates the thermoregulatory response of CNS leptin signaling by evaluating food intake, body weight, core temperature (TC), and spontaneous physical activity (SPA) in response to either exogenous leptin or 4-day cold exposure (4°C) in male POMC-Ptp1b-deficient mice compared with wild-type controls. POMC-Ptp1b Ϫ/Ϫ mice were hypersensitive to leptin-induced food intake and body weight suppression compared with wild types, yet they displayed similar leptin-induced increases in TC. Interestingly, POMC-Ptp1b Ϫ/Ϫ mice had increased BAT weight and elevated plasma triiodothyronine (T3) levels in response to a 4-day cold challenge, as well as reduced SPA 24 h after cold exposure, relative to controls. These data show that PTP1B in POMC neurons plays a role in short-term cold-induced reduction of SPA and may influence cold-induced thermogenesis via enhanced activation of the thyroid axis.protein tyrosine phosphatase 1B; proopiomelanocortin; phosphatase; leptin; energy expenditure; thermogenesis; thyroid THE ADIPOSE TISSUE-DERIVED HORMONE LEPTIN mediates effects on energy balance via suppression of food intake and stimulation of energy expenditure (for review, see Ref. 6). Within the arcuate nucleus (ARC) of the hypothalamus, two distinct populations of neurons synthesize either agouti-related protein (AgRP) or proopiomelanocortin (POMC) and mediate opposing effects on energy balance. Circulating leptin activates these and other central nervous system (CNS) neurons, leading to decreased food intake and increased energy expenditure, in part through simultaneous suppression of AgRP signaling and stimulation of POMC signaling. Deletion of the leptin receptor (LepR) in POMC neurons (POMC-Cre: LepR loxP/loxP ) results in increased body weight and adiposity, hyperleptinemia, and altered hypothalamic neuropeptide expression (1, 45), demonstrating the importance of POMC neurons to energy balance control.In addition to leptin's effects on food intake and energy expenditure, the hormone also regulates thermogenesis and loco...

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“…The absence of TTR did not influence the expected increase in BAT DII mRNA upon exposure to cold. With respect to UCP1, acute (Bianco et al 2002) and chronic (Zaninovich et al 2002, Liebig et al 2004) exposure to cold is described as inducing mRNA levels and protein activity. In accord, in our experiment, the levels of UCP1 BAT mRNA were increased in both wild-type and TTR-null mice 1 month (chronic) after exposure to cold, although the increase is relatively mild compared with the changes described after acute exposure.…”

Section: Figurementioning

confidence: 99%

“…In fact, hypothyroid rodents (Bianco et al 2002, Zaninovich et al 2002 and mice depleted of all thyroid hormone receptors (Golozoubova et al 2004) are cold intolerant. With the present data we clearly show that TTR does not seem to play a buffer or storage role useful for conditions of increased hormone demand.…”

Section: Figurementioning

confidence: 99%

Transthyretin is not necessary for thyroid hormone metabolism in conditions of increased hormone demand

Sousa¹,

Escobar²,

Oliveira³

et al. 2005

Journal of Endocrinology

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Thyroid hormones circulate in blood mainly bound to plasma proteins. Transthyretin is the major thyroxine plasma carrier in mice. Studies in transthyretin-null mice revealed that the absence of transthyretin results in euthyroid hypothyroxinemia and normal thyroid hormone tissue distribution, with the exception of the choroid plexus in the brain. Therefore, transthyretin does not influence normal thyroid hormone homeostasis under standard laboratory conditions. To investigate if transthyretin has a buffer/storage role we challenged transthyretin-null and wild-type mice with conditions of increased hormone demand: (i) exposure to cold, which elicits thermogenesis, a process that requires thyroid hormones; and (ii) thyroidectomy, which abolishes thyroid hormone synthesis and secretion and induces severe hypothyroidism. Transthyretin-null mice responded as the wild-type both to changes induced by stressful events, namely in body weight, food intake and thyroid hormone tissue content, and in the mRNA levels of genes whose expression is altered in such conditions. These results clearly exclude a role for transthyretin in thyroid hormone homeostasis even under conditions of increased hormone demand.

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Brown fat thermogenesis in cold-acclimated rats is not abolished by the suppression of thyroid function

Cited by 27 publications

References 42 publications

Neuronal UCP1 expression suggests a mechanism for local thermogenesis during hibernation

Neuronal UCP1 expression suggests a mechanism for local thermogenesis during hibernation

Deficiency of PTP1B in POMC neurons leads to alterations in energy balance and homeostatic response to cold exposure

Transthyretin is not necessary for thyroid hormone metabolism in conditions of increased hormone demand

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