Adipose tissue-selective ablation of ADAM10 results in divergent metabolic phenotypes following long-term dietary manipulation.

A Disintegrin And Metalloproteinase domain-containing protein 10 (ADAM10), is involved in several metabolic and inflammatory pathways. We speculated that ADAM10 plays a modulatory role in adipose tissue inflammation and metabolism. To this end, we studied adipose tissue-specific ADAM10 knock-out mice (aKO).

Proton Pump Inhibitors Do Not Affect the Bioavailability of a Novel Liquid Formulation of Levothyroxine.

Objective: This study evaluates the impact of a representative proton pump inhibitor (PPI) (omeprazole), administered simultaneously or staggered, on the pharmacokinetics of levothyroxine (LT4) solution (Tirosint-SOL).

Methods: This was a randomized, 3-way crossover, comparative bioavailability study in 36 healthy adults under fasting conditions. Omeprazole 40 mg delayed-release capsule was administered once daily from Day 1 to 6 (mornings, Treatment-A; evenings, Treatment-B; none, Treatment-C) to increase and stabilize gastric pH.

Insulin Edema Associated With Glargine.

Insulin edema is a poorly understood complication of insulin therapy. It has been reported in patients with both type 1 and 2 diabetes mellitus and typically occurs in patients with newly diagnosed or poorly controlled diabetes mellitus either after initiation or intensification of insulin therapy. A 20-year-old man presented with anorexia, polydipsia, and weight loss.

Overexpression of ORMDL3 confers sexual dimorphism in diet-induced non-alcoholic steatohepatitis.

Objective: The bioactive sphingolipid metabolites ceramide and sphingosine-1-phosphate (S1P) accumulate with overnutrition and have been implicated in non-alcoholic steatohepatitis (NASH) development. ORMDL3, a negative regulator of the rate-limiting step in ceramide biosynthesis, has been identified as an obesity-related gene. Therefore, we assessed the role of ORMDL3 in diet-induced obesity and development of NASH.

Unexplained Cachexia as a Presenting Symptom of Pheochromocytoma in a Geriatric Patient.

Pheochromocytomas are rare neuroendocrine tumors that may secrete catecholamines, resulting in a wide array of clinical symptoms. While patients classically present with hypertension, headache, diaphoresis, and flushing, these symptoms are present in only 40% of cases. Here, we describe a 70-year-old woman whose predominant symptom was unexplained severe weight loss over a 12-month period associated with fatigue, anxiety, and palpitations at her endocrinologist and geriatrician visits.

Efficacy of Levothyroxine Sodium Soft Gelatin Capsules in Thyroidectomized Patients Taking Proton Pump Inhibitors: An Open-Label Study.

Treatment with proton pump inhibitors (PPIs) and antacids affects the gastrointestinal absorption of levothyroxine sodium (LT4) tablets. Patients with hypothyroidism taking LT4 and PPIs or antacids, thus, require appropriate monitoring. The objective of this study was to determine whether a soft gelatin capsule of LT4 (Tirosint) would obviate the effect of PPIs on LT4 absorption.

Thyroid hormone action and liver disease, a complex interplay.

Thyroid hormone action is involved in virtually all physiological processes. It is well known that the liver and thyroid are intimately linked, with thyroid hormone playing important roles in de novo lipogenesis, beta-oxidation (fatty acid oxidation), cholesterol metabolism, and carbohydrate metabolism. Clinical and mechanistic research studies have shown that thyroid hormone can be involved in chronic liver diseases, including alcohol-associated or NAFLD and HCC.

Critical Approach to Hypothyroid Patients With Persistent Symptoms.

Hypothyroidism is a common condition, and numerous studies have been published over the last decade to assess the potential risks associated with this disorder when inappropriately treated. The standard of care for treatment of hypothyroidism remains levothyroxine (LT4) at doses to achieve biochemical and clinical euthyroidism. However, about 15% of hypothyroid patients experience residual hypothyroid symptoms.

Selective adipocyte loss of Angiopoietin-2 prompts female-specific obesity and metabolic syndrome.

Thermogenic fat differentiation and function can be promoted through multiple pathways, resulting in a common cell phenotype characterized by the expression of Uncoupling Protein-1 and the ability to dissipate energy, but local and systemic stimuli are necessary to promote adequate thermogenic fat vascularization, which is a precondition for the transport of substrate and the dissipation of heat. Angiopoietin-2 is an important driver of vascularization, and its transcription is in part promoted by estrogen signaling. In this study we demonstrate that adipose tissue-specific knock out of Angiopoietin-2 causes a female-specific reduced thermogenic fat differentiation and function, resulting in obesity and impaired glucose tolerance with end-organ features consistent with metabolic syndrome.

A Novel Levothyroxine Solution Results in Similar Bioavailability Whether Taken 30 or Just 15 Minutes Before a High-Fat High-Calorie Meal.

Levothyroxine (LT4) sodium is a standard treatment for hypothyroidism. Its absorption and bioavailability when taken as a tablet have been shown to be significantly decreased with concomitant food ingestion. Therefore, LT4 formulations are recommended to be taken on an empty stomach, at least 30, ideally 60, minutes before breakfast, potentially affecting adherence to therapy.

Acute Effects of Liothyronine Administration on Cardiovascular System and Energy Metabolism in Healthy Volunteers.

Context: The pharmacokinetics of liothyronine causes concerns for cardiovascular toxicity. While the effects of sustained increase in serum T3 concentrations are well described, little is known on the effects of acute changes in T3 concentrations due to rapid action of thyroid hormone.

Objective: To assess the clinical relevance of transient increase of T3 levels on cardiovascular system and energy metabolism.

Midpoint of energy intake, non-fasting time and cardiorespiratory fitness in heart failure with preserved ejection fraction and obesity.

Background: Delayed time of evening meal is associated with favorable cardiorespiratory fitness (CRF) in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. It is unknown, however, if increasing daily non-fasting time or delaying the midpoint of energy intake may also be associated with CRF.

Objective: Our aim was to examine whether a longer non-fasting time, delayed midpoint of energy intake, or both, are associated with greater CRF in patients with HFpEF and obesity.

Metabolic Phenotyping in Mice with NASH Using Indirect Calorimetry.

Obesity caused by caloric overload has assumed epidemic proportions. Obesity is frequently associated with metabolic dysfunctions, such as type 2 diabetes, non-alcoholic steatohepatitis (NASH), cardiovascular diseases, and cancer. Metabolic phenotyping is a set of techniques for studying metabolic dysfunction and behavior information including energy expenditure, body weight gain, glucose homeostasis, and lipid profile.

Differential fuel utilization in liver transplant recipients and its relationship with non-alcoholic fatty liver disease.

Unlabelled: Metabolic flexibility is the ability to match biofuel availability to utilization. Reduced metabolic flexibility, or lower fatty acid (FA) oxidation in the fasted state, is associated with obesity. The present study evaluated metabolic flexibility after liver transplantation (LT).

Time of eating and cardiorespiratory fitness in patients with heart failure with preserved ejection fraction and obesity.

Background And Aims: Our objective was to examine the impact of caloric intake before or after the mean time of evening meal on cardiorespiratory fitness (CRF) in patients with heart failure with preserved ejection fraction (HFpEF) and obesity.

Methods And Results: Twelve patients with HFpEF and obesity completed a cardiorespiratory exercise test to measure CRF, defined as peak oxygen consumption (VO). Three five-pass 24-h dietary recalls were performed for each participant and mean evening meal time was determined for each participant individually as well as the group.

Identification of the transgene insertion site for an adipocyte-specific adiponectin-cre model and characterization of the functional consequences.

The transgenic mouse is widely used in the development of adipocyte-specific genetic manipulations for the study of obesity and type 2 diabetes. In the process of developing a new mouse model utilizing the adipocyte selective transgenic mouse, strong genetic linkage between a gene of interest, , and the transgene was discovered. Whole-genome sequencing of the transgenic mouse model identified the genomic insertion site within the gene locus on chromosome 9 and this insertion causes a significant decrease in gene expression in adipose tissue.

Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document.

Fourteen clinical trials have not shown a consistent benefit of combination therapy with levothyroxine (LT4) and liothyronine (LT3). Despite the publication of these trials, combination therapy is widely used and patients reporting benefit continue to generate patient and physician interest in this area. Recent scientific developments may provide insight into this inconsistency and guide future studies.

Weight Gain After Thyroidectomy: A Systematic Review and Meta-Analysis.

Context: Weight gain is a major driver of dissatisfaction and decreased quality of life in patients with hypothyroidism. Data on the changes in body weight following thyroidectomy are conflicting.

Objective: To perform a systematic review of the literature and a meta-analysis of weight changes following total thyroidectomy.

Adipocyte ADAM17 plays a limited role in metabolic inflammation.

The role of ADAM17, its substrates, and its natural inhibitor has been well studied in the context of inflammation, including metabolic inflammation, with mixed results. Previous studies examining global knockdown models and ADAM17 inhibition using overexpression of endogenous ADAM17 inhibitors have shown improved metabolic health and decreased metabolic inflammation. However, there have been no studies examining the role of adipocyte ADAM17 using models.

An appraisal of whole-room indirect calorimeters and a metabolic cart for measuring resting and active metabolic rates.

Whole-room indirect calorimeters (WRICs) have traditionally been used for real-time resting metabolic rate (RMR) measurements, while metabolic rate (MR) during short-interval exercises has commonly been measured by metabolic carts (MCs). This study aims to investigate the feasibility of incorporating short-interval exercises into WRIC study protocols by comparing the performance of WRICs and an MC. We assessed the 40-min RMR of 15 subjects with 2-day repeats and the 10-15 min activity MR (AMR) of 14 subjects at three intensities, using a large WRIC, a small WRIC, and an MC.

Combination Therapy for Hypothyroidism: Rationale, Therapeutic Goals, and Design.

Hypothyroidism is a common condition with a wide spectrum of etiologies and clinical manifestations. While the majority of patients affected by hypothyroidism respond well to levothyroxine, some patients do not and complain of symptoms despite adequate replacement. There is evidence in experimental models of hypothyroidism that levothyroxine alone may not be able to deliver an adequate amount of T3 to all the tissues targeted by the hormonal action, while liothyronine/levothyroxine combination therapy can.