T3 and Triac inhibit leptin secretion and expression in brown and white rat adipocytes

Medina-Gómez, Gema; Calvo, Rosa-Maria; Obregón, Marı́a-Jesús

doi:10.1016/j.bbalip.2004.01.007

Cited by 24 publications

(7 citation statements)

References 49 publications

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“…Effects of the lowest TRIAC dose on LPL were observed in BAT and WAT, although in opposite directions, but not in heart. For leptin, the inhibition was observed using T 3 and TRIAC, in agreement with previous results in cultured brown and white adipocytes (33), suggesting that LPL and leptin could contribute to increased energy expenditure or lipid mobilization in our model. TRIAC (specially the low dose) had almost no effect in D1 activities, except in kidney.…”

supporting

confidence: 80%

Thermogenic effect of triiodothyroacetic acid at low doses in rat adipose tissue without adverse side effects in the thyroid axis

Medina-Gómez

Calvo²,

Obregón³

2008

American Journal of Physiology-Endocrinology and Metabolism

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Medina-Gomez G, Calvo RM, Obregon M-J. Thermogenic effect of triiodothyroacetic acid at low doses in rat adipose tissue without adverse side effects in the thyroid axis. Am J Physiol Endocrinol Metab 294: E688-E697, 2008. First published February 19, 2008 doi:10.1152/ajpendo.00417.2007.-Triiodothyroacetic acid (TRIAC) is a physiological product of triiodothyronine (T 3) metabolism, with high affinity for T 3 nuclear receptors. Its interest stems from its potential thermogenic effects. Thus this work aimed 1) to clarify these thermogenic effects mediated by TRIAC vs. T 3 in vivo and 2) to determine whether they occurred predominantly in adipose tissues. To examine this, control rats were infused with equimolar T 3 or TRIAC doses (0.8 or 4 nmol ⅐ 100 g body wt Ϫ1 ⅐ day Ϫ1 ) or exposed for 48 h to cold. Both T 3 doses and only the highest TRIAC dose inhibited plasma and pituitary thyroid-stimulating hormone (TSH) and thyroxine (T 4) in plasma and tissues. Interestingly, the lower TRIAC dose marginally inhibited plasma T 4. T3 infusion increased plasma and tissue T 3 in a tissue-specific manner. The highest TRIAC dose increased TRIAC concentrations in plasma and tissues, decreasing plasma T 3. TRIAC concentrations in tissues were Ͻ10% those of T 3. Under cold exposure or high T3 doses, TRIAC increased only in white adipose tissue (WAT). Remarkably, only the lower TRIAC dose activated thermogenesis, inducing ectopic uncoupling protein (UCP)-1 expression in WAT and maximal increases in UCP-1, UCP-2, and lipoprotein lipase (LPL) expression in brown adipose tissue (BAT), inhibiting UCP-2 in muscle and LPL in WAT. TRIAC, T 3, and cold exposure inhibited leptin secretion and mRNA in WAT. In summary, TRIAC, at low doses, induces thermogenic effects in adipose tissues without concomitant inhibition of TSH or hypothyroxinemia, suggesting a specific role regulating energy balance. This selective effect of TRIAC in adipose tissues might be considered a potential tool to increase energy metabolism. thermogenesis; leptin; lipoprotein lipase; deiodinases THE MAIN PATHWAYS of triiodothyronine (T 3 ) metabolism are deiodination, conjugation with glucuronides and sulfates, and modification of the alanine chain producing acetic and propionic metabolites. Triiodothyroacetic acid (TRIAC, also known as Tiratricol) is a physiological product of T 3 metabolism, derived by deamination and oxidative decarboxylation of the alanine chain (55). In humans, TRIAC production by the liver and other tissues accounts for ϳ14% of T 3 metabolism (17). This production is increased under certain physiological conditions, such as fasting (29). Serum TRIAC concentrations in humans are very low (42-140 pM) (17,35,38). The free fraction in serum is lower than that of T 3 , due to higher binding to plasma proteins, especially to transthyretin (18,35). TRIAC has a faster metabolic clearance rate and shorter half-life than T 3 in humans (35), due to its rapid hepatic metabolism, via the formation of sulfates and glucuronides, especially in humans (36, 51).

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confidence: 80%

Thermogenic effect of triiodothyroacetic acid at low doses in rat adipose tissue without adverse side effects in the thyroid axis

Medina-Gómez

Calvo²,

Obregón³

2008

American Journal of Physiology-Endocrinology and Metabolism

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“…On the other hand, T 3 induces a rise in the expression of genes coding for enzymes of lipogenesis (45,55) and stimulates food intake by acting directly on the ventromedial nucleus (41). This orexigenic effect is also achieved by the inhibition of leptin production (51). Taking the sum of these effects into account, the lower T 3 levels in RYGB-S rats would explain the reduction in fat pad mass, caloric intake, and body weight.…”

Section: Table 5 Feeding/metabolic Function-related Genes Showing DImentioning

confidence: 99%

Characterization of weight loss and weight regain mechanisms after Roux-en-Y gastric bypass in rats

Guijarro¹,

Suzuki²,

Chen³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Y gastric bypass (RYGB) is the most effective therapy for morbid obesity, but it has a ϳ20% failure rate. To test our hypothesis that outcome depends on differential modifications of several energy-related systems, we used our established RYGB model in Sprague-Dawley diet-induced obese (DIO) rats to determine mechanisms contributing to successful (RGYB-S) or failed (RYGB-F) RYGB. DIO rats were randomized to RYGB, sham-operated Obese, and sham-operated obese pair-fed linked to RYGB (PF) groups. Body weight (BW), caloric intake (CI), and fecal output (FO) were recorded daily for 90 days, food efficiency (FE) was calculated, and morphological changes were determined. D-Xylose and fat absorption were studied. Glucose-stimulated vagal efferent nerve firing rates of stomach were recorded. Gut, adipose, and thyroid hormones were measured in plasma. Mitochondrial respiratory complexes in skeletal muscle and expression of energy-related hypothalamic and fat peptides, receptors, and enzymes were quantified. A 25% failure rate occurred. RYGB-S, RYGB-F, and PF rats showed rapid BW decrease vs. Obese rats, followed by sustained BW loss in RYGB-S rats. RYGB-F and PF rats gradually increased BW. BW loss in RYGB-S rats is achieved not only by RYGB-induced decreased CI and increased FO, but also via sympathetic nervous system activation, driven by increased peptide YY, CRF, and orexin signaling, decreasing FE and energy storage, demonstrated by reduced fat mass associated with the upregulation of mitochondrial uncoupling protein-2 in fat. These events override the compensatory response to the drop in leptin levels aimed at conserving energy. food efficiency; gut and adipose hormones; mitochondria; obesity BARIATRIC OPERATIONS are currently the only treatment for morbid obesity (defined as a body mass index of 39 or greater or weight at least 50% above normal). Of the 180,000 -200,000 bariatric operations performed in 2006, ϳ80% were Roux-en-Y gastric bypass (RYGB). RYGB also reverses and ameliorates the major cardiovascular and metabolic risk factors, including Type 2 diabetes mellitus and hyper-and dyslipidemia (12, 72), reduces the long-term mortality and morbidity associated with obesity, and decreases health care costs (15).Despite the success of the RYGB operation, 20% of patients "fail to maintain long-term weight loss." Non-surgically related failure usually occurs within the first three postoperative years (12), suggesting a metabolic-endocrine compensatory etiologic mechanism.Weight loss induced by RYGB occurs biphasically. Initially there is rapid weight loss lasting 1-3 yr, followed by prolonged weight stabilization (39). Both occur despite a gradual increase in caloric intake during the same period (72). Our RYGB model in diet-induced obese Sprague-Dawley rats (52) also shows a postoperative biphasic weight change pattern. In this model, ϳ10 -13 rat days is equivalent to 1 human year (62), thus allowing us to follow rats postoperatively for a considerably long time compared with human subjects.Conventional surgical b...

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“…It has been postulated that the increased TA 3 levels are responsible for the suppression of TSH observed under these conditions despite low serum TH levels. In addition, TA 3 potently suppresses leptin secretion by rat brown and white adipocytes, and since leptin stimulates TSH secretion this may induce a further decline in TSH levels (Medina-Gomez et al 2004). …”

Section: Regulation and Role Of Tamentioning

confidence: 99%

Triiodothyroacetic acid in health and disease

Groeneweg

Peeters

Visser

et al. 2017

Journal of Endocrinology

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Thyroid hormone (TH) is crucial for development and metabolism of many tissues. The physiological relevance and therapeutic potential of TH analogs have gained attention in the field for many years. In particular, the relevance and use of 3,3′,5-triiodothyroacetic acid (Triac, TA 3 ) has been explored over the last decades. Although TA 3 closely resembles the bioactive hormone T 3 , differences in transmembrane transport and receptor isoformspecific transcriptional activation potency exist. For these reasons, the application of TA 3 as a treatment for resistance to TH (RTH) syndromes, especially MCT8 deficiency, is topic of ongoing research. This review is a summary of all currently available literature about the formation, metabolism, action and therapeutic applications of TA 3 .

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T3 and Triac inhibit leptin secretion and expression in brown and white rat adipocytes

Cited by 24 publications

References 49 publications

Thermogenic effect of triiodothyroacetic acid at low doses in rat adipose tissue without adverse side effects in the thyroid axis

Thermogenic effect of triiodothyroacetic acid at low doses in rat adipose tissue without adverse side effects in the thyroid axis

Characterization of weight loss and weight regain mechanisms after Roux-en-Y gastric bypass in rats

Triiodothyroacetic acid in health and disease

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