Leptin Decreases Energy Expenditure Despite Increased Thyroid Hormone in Patients with Lipodystrophy

2021 ◽  
Author(s):  
Andrew Grover ◽  
Emmanuel Quaye ◽  
Robert J Brychta ◽  
John Christensen ◽  
Megan S Startzell ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Energy Expenditure ◽  
Resting Energy Expenditure ◽  
Free T4 ◽  
Autonomic Nervous System Activity ◽  
Free T3 ◽  
Mediated Effects ◽  
Nervous System Activity ◽  
Before And After ◽  
Randomized Crossover Study

Abstract Context Leptin is an adipokine that signals energy sufficiency. In rodents, leptin deficiency decreases energy expenditure (EE), which is corrected following leptin replacement. In humans, data are mixed regarding leptin-mediated effects on EE. Objective To determine the effects of metreleptin on EE in patients with lipodystrophy. Design, setting, and patients Non-randomized crossover study of 25 patients with lipodystrophy (NIH, 2013-2018). Intervention The initiation cohort consisted of 17 patients without prior exposure to metreleptin, studied before and after 14 days of metreleptin. The withdrawal cohort consisted of 8 previously metreleptin-treated patients, studied before and after 14 days of metreleptin withdrawal. Main outcomes 24-hour energy expenditure (TEE), resting energy expenditure (REE), autonomic nervous system activity (heart rate variability, HrV), plasma free T3, free T4, epinephrine, norepinephrine, and dopamine. Results In the initiation cohort, TEE and REE decreased by 5.0% (121±152 kcal/day; p=0.006) and 5.9% (120±175 kcal/day; p=0.02). Free T3 increased by 19.4% (40±49 pg/dL; p=0.01). No changes in catecholamines or HrV were observed. In the withdrawal cohort, free T3 decreased by 8.0% (p=0.04), free T4 decreased by 11.9% (p=0.002), and norepinephrine decreased by 34.2% (p=0.03), but no changes in EE, epinephrine, dopamine, or HrV were observed. Conclusions Metreleptin initiation decreased EE in patients with lipodystrophy, but no changes were observed after metreleptin withdrawal. Thyroid hormone was higher on metreleptin in both initiation and withdrawal cohorts. Decreased EE after metreleptin in lipodystrophy may result from reductions in energy-requiring metabolic processes that counteract increases in EE via adipose tissue-specific neuroendocrine and adrenergic signaling.

scholarly journals Resting Energy Expenditure and Cold Induced Thermogenesis in Patients with Overt Hyperthyroidism

2021 ◽  
Author(s):  
Claudia Irene Maushart ◽  
Jaël Rut Senn ◽  
Rahel Catherina Loeliger ◽  
Judith Siegenthaler ◽  
Fabienne Bur ◽  
...  
Keyword(s):  
Body Composition ◽  
Energy Expenditure ◽  
Skin Temperature ◽  
Cold Exposure ◽  
Resting Energy Expenditure ◽  
Free T4 ◽  
Free T3 ◽  
Euthyroid State ◽  
Overt Hyperthyroidism ◽  
Resting Energy

Abstract Context Thyroid hormone is crucial for the adaptation to cold. Objective To evaluate the effect of hyperthyroidism on resting energy expenditure (REE), cold-induced thermogenesis (CIT) and changes in body composition and weight. Design Prospective cohort study. Setting Endocrine outpatient clinic at tertiary referral center. Patients Eighteen patients with overt hyperthyroidism. Main Outcome Measures We measured REE during hyperthyroidism, after restoring euthyroid TH levels and after 3 months of normal thyroid function. In fourteen patients energy expenditure (EE) was measured before and after a mild cold exposure of two hours and CIT was the difference between EEcold and EEwarm. Skin temperatures at eight positions were recorded during the study visits. Body composition was assessed by dual X-ray absorption. Results Free T4 (fT4) and free T3 (fT3) decreased significantly over time (fT4, p=0.0003; fT3, p=0.0001). REE corrected for lean body mass (LBM) decreased from 42 ± 6.7 kcal/24h/kg LBM in the hyperthyroid to 33±4.4 kcal/24h/kg LBM (-21%, p<0.0001 vs hyperthyroid) in the euthyroid state and three months later to 33 ± 5.2 kcal/24h/kg LBM (-21%, p=0.0022 vs. hyperthyroid, overall p<0.0001). Free T4 (p=0.0001) and free T3 (p<0.0001) were predictors of REE. CIT did not change from the hyperthyroid to the euthyroid state (p=0.96). Hyperthyroidism led to increased skin temperature at warm ambient conditions but did not alter core body temperature, nor skin temperature after cold exposure. Weight regain and body composition were not influenced by REE and CIT during the hyperthyroid state. Conclusions CIT is not increased in patients with overt hyperthyroidism.

scholarly journals Leptin Decreases Energy Expenditure but Increases Thyroid Hormone in Patients With Lipodystrophy

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A19-A20
Author(s):  
Emmanuel Quaye ◽  
Andrew Grover ◽  
Robert Brychta ◽  
John Christensen ◽  
Megan S Startzell ◽  
...  
Keyword(s):  
Weight Loss ◽  
Thyroid Hormone ◽  
Energy Expenditure ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Free T4 ◽  
Free T3 ◽  
Healthy Humans ◽  
Leptin Deficiency ◽  
Period 2

Abstract Leptin is an adipokine that signals energy sufficiency. In rodents, leptin deficiency is associated with decreased body temperature and energy expenditure (EE), which is reversed with leptin replacement. Leptin’s role in EE in humans is unclear; however, one study of 10% weight-reduced healthy subjects suggested that leptin replacement to pre-weight loss levels restored the decline in EE, thyroid hormone, and catecholamines associated with weight loss. Patients with lipodystrophy (LD) are characterized by deficiency of adipose tissue and can serve as models to study effects of leptin deficiency and replacement in humans. We hypothesized that treatment with recombinant leptin (metreleptin) in patients with LD would increase EE, thyroid hormone, and catecholamines. We conducted a non-randomized crossover study of 25 patients with LD who were hospitalized for 19 days on an iso-caloric diet. The initiation cohort consisted of 17 patients with no prior exposure to metreleptin, who were first studied for 5 days without metreleptin (period 1), then were treated with metreleptin for 14 days (period 2). The withdrawal cohort consisted of 8 previously metreleptin-treated patients who were continued on metreleptin for the first 5 days of the study (period 1), then were taken off metreleptin for 14 days (period 2). At the end of each period, we measured 24-hour EE (TEE) and resting EE (REE) using indirect calorimetry and free T3, T4, epinephrine, norepinephrine and dopamine after an 8–12 hour fast. In the leptin initiation cohort, TEE and REE decreased from 2402±383 kcal/day and 1805±332 kcal/day to 2272±396 kcal/day (p=0.003) and 1688±318 kcal/day (p=0.03), respectively. Free T3 increased from median (IQR) 248 (200, 270) pg/mL to 295 (259, 315) (p=0.006). No changes in catecholamines were observed in the initiation cohort. In the withdrawal cohort, free T3 decreased from 295 (267, 331) pg/mL to 265 (237, 323) (p=0.008), free T4 decreased from 1.2 ±0.2 ng/dL to 1.0±0.2 (p=0.002), and norepinephrine decreased from 191±70 pg/mL to 112±47 (p=0.03) after metreleptin withdrawal. No changes in EE, epinephrine or dopamine were observed in the withdrawal cohort. Contrary to previous studies in rodents and healthy humans, we found that introduction of metreleptin reduced EE in patients with LD. Consistent with rodent and prior human data, patients with LD had increased thyroid hormone on metreleptin, which would be expected to increase EE. The discrepancy in EE compared to other models may be due to metreleptin-induced correction of severe metabolic derangements in LD, including reduction in energy-requiring processes such as de novo lipogenesis and gluconeogenesis. These changes may offset increases in leptin-induced mediators of increased EE, such as thyroid hormone.

scholarly journals Alterations in endothelium-associated proteins and serum thyroid hormone concentrations in anorexia nervosa

1992 ◽  
Vol 68 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Gen Komaki ◽  
Hajime Tamai ◽  
Toshio Mukuta ◽  
Nobuyuki Kobayashi ◽  
Kenji Mori ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Weight Gain ◽  
Thyroid Hormone ◽  
Plasma Concentrations ◽  
Free T4 ◽  
Free T3 ◽  
Before And After ◽  
Associated Proteins ◽  
Serum T3 ◽  
Serum Thyroid Hormone

Plasma concentrations of endothelium-associated proteins (EAP) (plasma fibronectin (PFN), angio-tensin-converting enzyme, factor VIII-related antigen (F VIII-R:Ag)) and tissue plasminogen activator and serum thyroid hormone concentrations were studied in nine patients with anorexia nervosa (AN), before and after weight gain. Before weight gain (-35.9 (se 2.3)% of standard body-weight) PFN was significantly reduced and F VIII-R:Ag was significantly increased in AN patients compared with the concentrations in control subjects (211.5 (se 14.9)v.274.7 (se 16.6) μg/ml,P< 0.05; 129.2 (se 14.1)v.88.2 (se 9.7)%,P<0.05 respectively). Serum triiodothyronine (T3) and free T3 levels were also significantly lower before weight gain in AN patients (0.85 (se 0.07)v.1.53 (se 0.08) nmol/l,P< 0.001; 2.57 (se 0.23)v.5.31 (se 0.34) pmol/l,P< 0.001 respectively), although serum thyroxine (T4), free T4, and thyrotropin concentrations were within the normal range throughout the study periods. Following weight gain, PFN and F VIII-R: Ag concentrations normalized as did the thyroid hormone levels. The incremental changes in PFN levels correlated significantly with those in serum thyroid hormone concentrations (T3,r0.79,P<0.01; free T3,r0.84,P< 0.01). These findings suggest that PFN levels may be directly related to serum T3 concentrations in AN patients.

scholarly journals Rescue pre-operative treatment with Lugol’s solution in uncontrolled Graves’ disease

2017 ◽  
Vol 6 (4) ◽  
pp. 200-205 ◽  
Author(s):  
Jan Calissendorff ◽  
Henrik Falhammar
Keyword(s):  
Heart Rate ◽  
Thyroid Hormone ◽  
Side Effects ◽  
Definitive Treatment ◽  
Graves Disease ◽  
Free T4 ◽  
Hormone Levels ◽  
Free T3 ◽  
Adherence To Medication ◽  
Thyroid Hormone Levels

Background Graves’ disease is a common cause of hyperthyroidism. Three therapies have been used for decades: pharmacologic therapy, surgery and radioiodine. In case of adverse events, especially agranulocytosis or hepatotoxicity, pre-treatment with Lugol’s solution containing iodine/potassium iodide to induce euthyroidism before surgery could be advocated, but this has rarely been reported. Methods All patients hospitalised due to uncontrolled hyperthyroidism at the Karolinska University Hospital 2005–2015 and treated with Lugol’s solution were included. All electronic files were carefully reviewed manually, with focus on the cause of treatment and admission, demographic data, and effects of iodine on thyroid hormone levels and pulse frequency. Results Twenty-seven patients were included. Lugol’s solution had been chosen due to agranulocytosis in 9 (33%), hepatotoxicity in 2 (7%), other side effects in 11 (41%) and poor adherence to medication in 5 (19%). Levels of free T4, free T3 and heart rate decreased significantly after 5–9 days of iodine therapy (free T4 53–20 pmol/L, P = 0.0002; free T3 20–6.5 pmol/L, P = 0.04; heart rate 87–76 beats/min P = 0.0007), whereas TSH remained unchanged. Side effects were noted in 4 (15%) (rash n = 2, rash and vomiting n = 1, swelling of fingers n = 1). Thyroidectomy was performed in 26 patients (96%) and one was treated with radioiodine; all treatments were without serious complications. Conclusion Treatment of uncontrolled hyperthyroidism with Lugol’s solution before definitive treatment is safe and it decreases thyroid hormone levels and heart rate. Side effects were limited. Lugol’s solution could be recommended pre-operatively in Graves’ disease with failed medical treatment, especially if side effects to anti-thyroid drugs have occurred.

Thermogenic effect of thyroid hormones: interactions with epinephrine and insulin.

1990 ◽  
Vol 259 (3) ◽  
pp. E305
Author(s):  
V Piolino ◽  
K J Acheson ◽  
M J Müller ◽  
N Jeanprêtre ◽  
A G Burger ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Thyroid Hormones ◽  
Basal Insulin ◽  
Plasma Insulin ◽  
Resting Energy Expenditure ◽  
Fat Free Mass ◽  
Short Term ◽  
Epinephrine Infusion ◽  
Before And After ◽  
Basal Plasma

The interactions between thyroid hormones, epinephrine, and insulin in the regulation of energy expenditure were investigated in a group of healthy young men before and after thyroxine (T4) treatment (300 micrograms/day for 14 days) at basal plasma insulin concentrations and during hypoinsulinemia with and without epinephrine infusion (0.05 micrograms.kg fat-free mass-1.min-1). T4 treatment induced moderate hyperthyroidism and increased resting energy expenditure (RMR). The effect was more pronounced during short-term hypoinsulinemia, but hypoinsulinemia by itself did not influence RMR. Epinephrine infusion caused a significant increase in energy expenditure. The effect was most pronounced at hypoinsulinemia and with T4 treatment. Hypoinsulinemia and T4 treatment were not additive in their effects. We conclude that basal insulin concentrations mask some of the thermogenic effects of thyroid hormones and epinephrine. Thus insulin antagonism may suppress some of the thermogenic actions of thyroid hormones and epinephrine.

Sign in / Sign up

Export Citation Format

Share Document