Triiodothyronine induces lipid oxidation and mitochondrial biogenesis in rat Harderian gland

Santillo, Alessandra; Burrone, Lavinia; Falvo, Sara; Senese, Rosalba; Lanni, Antonia; Baccari, Gabriella Chieffi

doi:10.1530/joe-13-0127

Cited by 15 publications

(11 citation statements)

References 47 publications

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“…The mitochondrial data here presented suggest that THs stimulate intraepidermal mitochondrial biogenesis (Supplementary Figure S3) as they do in many other tissues, including human hair follicles (Cioffi et al, 2013;Lee et al, 2012;Marin-Garcia, 2010;Santillo et al, 2013;Vakitus et al, 2015;Vidali et al, 2014), via a sirt1-PGC1α-mediated pathway. Also, both THs decreased mTORC1/2, whose inhibition is involved in mitochondrial biogenesis and reportedly restores a more juvenile phenotype and increased life span (Chiao et al, 2016;Evangelisti et al, 2016;Johnson et al, 2013).…”

Section: Discussionsupporting

confidence: 52%

Thyroid Hormones Enhance Mitochondrial Function in Human Epidermis

Vidali

Chéret

Giesen

et al. 2016

Journal of Investigative Dermatology

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Since it is unknown whether thyroid hormones (THs) regulate mitochondrial function in human epidermis, we treated organ-cultured human skin, or isolated cultured human epidermal keratinocytes, with triiodothyronine (100 pmol/L) or thyroxine (100 nmol/L). Both THs significantly increased protein expression of the mitochondrially encoded cytochrome C oxidase I (MTCO1), complex I activity, and the number of perinuclear mitochondria. Triiodothyronine also increased mitochondrial transcription factor A (TFAM) protein expression, and thyroxine stimulated complex II/IV activity. Increased mitochondrial function can correlate with increased reactive oxygen species production, DNA damage, and accelerated tissue aging. However, THs neither raised reactive oxygen species production or matrix metalloproteinase-1, -2 and -9 activity nor decreased sirtuin1 (Sirt1) immunoreactivity. Instead, triiodothyronine increased sirtuin-1, fibrillin-1, proliferator-activated receptor-gamma 1-alpha (PGC1α), collagen I and III transcription, and thyroxine decreased cyclin-dependent kinase inhibitor 2A (p16(ink4)) expression in organ-cultured human skin. Moreover, TH treatment increased intracutaneous fibrillin-rich microfibril and collagen III deposition and decreased mammalian target of rapamycin (mTORC1/2) expression ex vivo. This identifies THs as potent endocrine stimulators of mitochondrial function in human epidermis, which down-regulates rather than enhance the expression of skin aging-related biomarkers ex vivo. Therefore, topically applied THs deserve further exploration as candidate agents for treating skin conditions characterized by reduced mitochondrial function.

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Section: Discussionsupporting

confidence: 52%

Thyroid Hormones Enhance Mitochondrial Function in Human Epidermis

Vidali

Chéret

Giesen

et al. 2016

Journal of Investigative Dermatology

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“…As the shift from glucose to fatty acid as a primary metabolic substrate represents a key event in cardiomyocyte maturation ( 14 ), we hypothesized that this intervention could facilitate maturation. Moreover, since T 3 can promote cardiomyocyte maturation ( 14 ), positively regulate cardiac genes ( MYH6, TNNI3, NKX2.5, SERCA , and RYR2 ) ( 14 – 16 ) and upregulate several rate-limiting enzymes in FAO and mitochondrial biogenesis ( 17 , 18 ), we hypothesized that this hormone could potentiate the maturation process. Indeed, compared to untreated control cells, treated cardiomyocytes exhibited a phenotype more consistent with mature cardiomyocytes, as evidenced by AP characteristics, sensitivity to isoproterenol, sarcomeric organization, proliferative activity, and expression levels of various ion channel and cardiac-specific genes.…”

Section: Discussionmentioning

confidence: 99%

“…Among these molecules, T 3 is known to positively regulate cardiac genes including MYH6, TNNI3, NKX2.5, SERCA , and RYR2 ( 14 – 16 ). More importantly, T 3 can promote fatty acid oxidation (FAO) by upregulating several rate-limiting enzymes in FAO and mitochondrial biogenesis ( 17 , 18 ), which may facilitate the metabolic switch from immature to mature cardiomyocytes.…”

Section: Introductionmentioning

confidence: 99%

Culture in Glucose-Depleted Medium Supplemented with Fatty Acid and 3,3′,5-Triiodo-l-Thyronine Facilitates Purification and Maturation of Human Pluripotent Stem Cell-Derived Cardiomyocytes

Lin

Stachel

et al. 2017

Front. Endocrinol.

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With recent advances in stem cell technology, it is becoming efficient to differentiate human pluripotent stem cells (hPSCs) into cardiomyocytes, which can subsequently be used for myriad purposes, ranging from interrogating mechanisms of cardiovascular disease, developing novel cellular therapeutic approaches, as well as assessing the cardiac safety profile of compounds. However, the relative inability to acquire abundant pure and mature cardiomyocytes still hinders these applications. Recently, it was reported that glucose-depleted culture medium supplemented with lactate can facilitate purification of hPSC-derived cardiomyocytes. Here, we report that fatty acid as a lactate replacement has not only a similar purification effect but also improves the electrophysiological characteristics of hPSC-derived cardiomyocytes. Glucose-depleted culture medium supplemented with fatty acid and 3,3′,5-Triiodo-l-thyronine (T3) was used during enrichment of hPSC-derived cardiomyocytes. Compared to untreated control cells, the treated cardiomyocytes exhibited enhanced action potential (AP) maximum upstroke velocity (as shown by a significant increase in dV/dtmax), action potential amplitude, as well as AP duration at 50% (APD50) and 90% (APD90) of repolarization. The treated cardiomyocytes displayed higher sensitivity to isoproterenol, more organized sarcomeric structures, and lower proliferative activity. Expression profiling showed that various ion channel and cardiac-specific genes were elevated as well. Our results suggest that the use of fatty acid and T3 can facilitate purification and maturation of hPSC-derived cardiomyocytes.

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“…To analyze StAR protein levels, mitochondrial fractions of testes were prepared as described (20,21). Cytosolic fractions were used to assay 3β-HSD, P450 aromatase, PCNA, Aurora B, SYCP3, and β-actin protein levels.…”

Section: Protein Extraction and Western Blot Analysismentioning

confidence: 99%

Mild Exercise Rescues Steroidogenesis and Spermatogenesis in Rats Submitted to Food Withdrawal

et al. 2020

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The present investigation was undertaken to increase our insight into the molecular basis of the physiological changes in rat testis induced by food withdrawal, and to clarify whether reduced testicular function can be ameliorated by mild exercise. Male rats were selected for four separate experiments. The first of each group was chow-fed, the second was chow-fed and submitted to exercise (5 bouts in total for 30 min at 15 m/min, and 0 • inclination), the third was submitted to food withdrawal (66 h) and the fourth was submitted to food withdrawal and to exercise. At the end of experiments, we investigated (i) serum and testicular sex hormone levels; (ii) protein levels of StAR, 3β-Hydroxysteroid dehydrogenase (3β-HSD) and P450 aromatase, which play a key role in steroid hormone biosynthesis; and (iii) protein levels of mitotic and meiotic markers of spermatogenesis in rats, in relation to testis morphology and morphometry. We found that mild exercise or food withdrawal alone induced a significant increase or decrease in both serum and testis testosterone levels, respectively. Interestingly, we found that these levels were brought back to basal levels when food withdrawal was combined with mild exercise. The changes in testosterone levels observed in our experimental groups correlated well with the expression of steroidogenic enzymes as well as with spermatogenic activity. With mild exercise the increased testosterone/17β-estradiol (T/E 2 ) ratio in the testis correlated with an increased spermatogenic activity. The T/E 2 ratio dropped in fasted rats and was significantly reversed when food withdrawal was combined with exercise. Histological and morphometric analyses confirmed that spermatogenic activity varied in concomitance with each experimental condition. Importantly, the testis and serum T/E 2 ratios correlated, confirming that exercise rescues the decline in food withdrawal-induced spermatogenesis. In conclusion, this study highlights that mild exercise normalizes the reduced spermatogenic activity caused by food withdrawal through the modulation of the steroidogenic pathway and restoring the T/E 2 ratio, underlining the beneficial effects of mild exercise on the prevention and/or amelioration of reduced testis function caused by restricted caloric intake.

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Triiodothyronine induces lipid oxidation and mitochondrial biogenesis in rat Harderian gland

Cited by 15 publications

References 47 publications

Thyroid Hormones Enhance Mitochondrial Function in Human Epidermis

Thyroid Hormones Enhance Mitochondrial Function in Human Epidermis

Culture in Glucose-Depleted Medium Supplemented with Fatty Acid and 3,3′,5-Triiodo-l-Thyronine Facilitates Purification and Maturation of Human Pluripotent Stem Cell-Derived Cardiomyocytes

Mild Exercise Rescues Steroidogenesis and Spermatogenesis in Rats Submitted to Food Withdrawal

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