Short-term antidepressant treatment has long-lasting effects, and reverses stress-induced decreases in bone features in rats.

Antidepressants are among the most-prescribed class of drugs in the world and though weight gain is a common outcome of antidepressant treatment, that effect is not well understood. We employed an animal model comprised of 2 weeks of chronic restraint stress with antidepressant treatment, followed by diet-induced obesity. We showed that short-term antidepressant treatment had long-lasting effects, not only leading to weight gain, but also enhancing trabecular and cortical bone features in rats; therefore, weight gain in this model was different from that of the classic diet-induced obesity.

MANAGEMENT OF ENDOCRINE DISEASE: Pitfalls on the replacement therapy for primary and central hypothyroidism in adults.

Hypothyroidism is one of the most common hormone deficiencies in adults. Most of the cases, particularly those of overt hypothyroidism, are easily diagnosed and managed, with excellent outcomes if treated adequately. However, minor alterations of thyroid function determine nonspecific manifestations.

Genetics of non-syndromic childhood obesity and the use of high-throughput DNA sequencing technologies.

Background: Childhood obesity is a serious public health problem associated with the development of several chronic diseases, such as type 2 diabetes mellitus, dyslipidemia, and hypertension. The elevated prevalence of obesity is mostly due to inadequate diet and lifestyle, but it is also influenced by genetic factors.

Objectives: To review recent advances in the field of the genetics of obesity.

Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study.

Objective: To compare the effects of a unique fixed combination levothyroxine/liothyronine (LT4/LT3) therapy in patients with primary hypothyroidism.

Subjects And Methods: This is a randomized, double-blind, crossover study. Adults with primary hypothyroidism (n = 32, age 42.

Role of the IL-1 Pathway in Dopaminergic Neurodegeneration and Decreased Voluntary Movement.

Interleukin-1 (IL-1), a proinflammatory cytokine synthesized and released by activated microglia, can cause dopaminergic neurodegeneration leading to Parkinson's disease (PD). However, it is uncertain whether IL-1 can act directly, or by exacerbating the harmful actions of other brain insults. To ascertain the role of the IL-1 pathway on dopaminergic neurodegeneration and motor skills during aging, we compared mice with impaired [caspase-1 knockout (casp1)] or overactivated IL-1 activity [IL-1 receptor antagonist knockout (IL-1ra)] to wild-type (wt) mice at young and middle age.

Is increased antidepressant exposure a contributory factor to the obesity pandemic?

Major depressive disorder (MDD) and obesity are both common heterogeneous disorders with complex aetiology, with a major impact on public health. Antidepressant prescribing has risen nearly 400% since 1988, according to data from the Centers for Disease Control and Prevention (CDC). In parallel, adult obesity rates have doubled since 1980, from 15 to 30 percent, while childhood obesity rates have more than tripled.

The Effects of Leptin Replacement on Neural Plasticity.

Leptin, an adipokine synthesized and secreted mainly by the adipose tissue, has multiple effects on the regulation of food intake, energy expenditure, and metabolism. Its recently-approved analogue, metreleptin, has been evaluated in clinical trials for the treatment of patients with leptin deficiency due to mutations in the leptin gene, lipodystrophy syndromes, and hypothalamic amenorrhea. In such patients, leptin replacement therapy has led to changes in brain structure and function in intra- and extrahypothalamic areas, including the hippocampus.

Association between circulating adipocytokine concentrations and microvascular complications in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of controlled cross-sectional studies.

Background: The adipocytokines leptin and adiponectin have been variously associated with diabetic microvascular complications. No comprehensive clinical data exist examining the association between adipocytokines and the presence of these complications.

Methods: This is a systematic review of cross-sectional studies comparing circulating adipocytokines in patients with type 2 diabetes mellitus (T2DM), with and without microvascular complications.

TSH levels are associated with increased risk of thyroid carcinoma in patients with nodular disease.

Introduction: Several studies have shown an increased risk of thyroid malignancies in patients with elevated TSH levels, even if these levels fell within the normal range. The aim of this study was to evaluate the relationship between TSH and risk of malignancy in patients with thyroid nodules.

Material And Methods: We included 622 patients with thyroid nodules evaluated by fine needle aspiration and/or thyroidectomy and diagnosed by cytology or histology.

New advances in the treatment of generalized lipodystrophy: role of metreleptin.

Recombinant methionyl human leptin or metreleptin is a synthetic leptin analog that has been trialed in patients with leptin-deficient conditions, such as leptin deficiency due to mutations in the leptin gene, hypothalamic amenorrhea, and lipodystrophy syndromes. These syndromes are characterized by partial or complete absence of adipose tissue and hormones derived from adipose tissue, most importantly leptin. Patients deficient in leptin exhibit a number of severe metabolic abnormalities such as hyperglycemia, hypertriglyceridemia, and hepatic steatosis, which can progress to diabetes mellitus, acute pancreatitis, and hepatic cirrhosis, respectively.

The use of dried blood spot sampling for the measurement of HbA1c: a cross-sectional study.

Background: The use of dried blood spot (DBS) sampling is an alternative to traditional venous blood collection, and particularly useful for people living in rural and remote areas, and for those who are infirm, house-bound or time-poor. The objective of this study was to assess whether the measurement of glycated haemoglobin A1c (HbA1c) in DBS samples provided comparative and acceptably precise results.

Methods: Venous and capillary blood samples were collected from 115 adult participants.

Temporal gene expression in the hippocampus and peripheral organs to endotoxin-induced systemic inflammatory response in caspase-1-deficient mice.

Objectives: Caspase-1 (casp1), a key protease involved in the systemic inflammatory response syndrome (SIRS), controls the brain expression of a set of eight genes: Nos2 and Ptgs2 (nitric oxide synthase 2 and prostaglandin-endoperoxide synthase 2, two inducible enzymes), Cxcl1 and Cxcl10 (C-X-C motif chemokine ligand 1 and ligand 10), Tgtp and Gbp2 (T cell-specific GTPase 1 and guanylate-binding protein 2, two GTPases), Adamts1 (a disintegrin-like and metallopeptidase with thrombospondin type 1 motif, 1, a metalloprotease) and Il1rn (interleukin-1 receptor antagonist). Our objective was to ascertain whether casp1 also controlled the peripheral expression of these genes and, if so, to compare their central versus peripheral patterns of gene expression in immune and endocrine tissues during SIRS.

Methods: Wild-type (wt) and casp1 knockout (casp1(-/-)) mice were injected with either saline or a high dose of endotoxin/lipopolysaccharide (LPS; 800 μg/mice i.

Evaluation of percutaneous ethanol injections in benign thyroid nodules.

Objective: The objective of this study was to evaluate the efficacy and safety of percutaneous ethanol injection (PEI) in the treatment of benign thyroid nodules.

Subjects And Methods: We evaluated 120 patients with benign thyroid nodules. Patients underwent evaluation of serum TSH and free T4, cervical ultrasound, and thyroid scintigraphy (in those with suppressed TSH levels).

Leptin replacement therapy for the treatment of non-HAART associated lipodystrophy syndromes: a meta-analysis into the effects of leptin on metabolic and hepatic endpoints.

The clinical manifestations of lipodystrophy syndromes (LS) are hypoleptinemia, hyperglycemia, insulin resistance, dyslipidemia and hepatic steatosis. Leptin replacement therapy (LRT) is effective at improving these pathologies. Currently, there are no data compiling the evidence from the literature, and demonstrating the effect of LRT in LS patients.

Whole exome sequencing of extreme morbid obesity patients: translational implications for obesity and related disorders.

Whole-exome sequencing (WES) is a new tool that allows the rapid, inexpensive and accurate exploration of Mendelian and complex diseases, such as obesity. To identify sequence variants associated with obesity, we performed WES of family trios of one male teenager and one female child with severe early-onset obesity. Additionally, the teenager patient had hypopituitarism and hyperprolactinaemia.

Leptin treatment: facts and expectations.

Leptin has key roles in the regulation of energy balance, body weight, metabolism, and endocrine function. Leptin levels are undetectable or very low in patients with lipodystrophy, hypothalamic amenorrhea, and congenital leptin deficiency (CLD) due to mutations in the leptin gene. For these patients, leptin replacement therapy with metreleptin (a recombinant leptin analog) has improved or normalized most of their phenotypes, including normalization of endocrine axes, decrease in insulin resistance, and improvement of lipid profile and hepatic steatosis.

Molecular pathways involved in the improvement of non-alcoholic fatty liver disease.

Unlabelled: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis are components of the metabolic syndrome. Serum leptin levels are elevated in obesity, but the role of leptin in the pathophysiology of the liver involvement is still unclear. To identify the effects and mechanisms by which leptin influences the pathogenesis of NAFLD, we performed epididymal white adipose tissue (eWAT) transplantation from congenic wild-type mice into the subcutaneous dorsal area of Lep(ob/ob) recipient mice and compared the results with those of the Lep(ob/ob) sham-operated mice.

Leptin therapy, insulin sensitivity, and glucose homeostasis.

Glucose homeostasis is closely regulated not only by insulin, but also by leptin. Both hormones act centrally, regulating food intake and adiposity in humans. Leptin has several effects on the glucose-insulin homeostasis, some of which are independent of body weight and adiposity.

Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications.

Leptin, the adipokine produced mainly by the white adipose tissue, plays important roles not only in the regulation of food intake, but also in controlling immunity and inflammation. It has been widely demonstrated that the absence of leptin leads to immune defects in animal and human models, ultimately increasing mortality. Leptin also regulates inflammation by means of actions on its receptor, that is widely spread across different immune cell populations.

Tumor necrosis factor-induced cerebral insulin resistance in Alzheimer's disease links numerous treatment rationales.

The evident limitations of the amyloid theory of the pathogenesis of Alzheimer's disease are increasingly putting alternatives in the spotlight. We argue here that a number of independently developing approaches to therapy-including specific and nonspecific anti-tumor necrosis factor (TNF) agents, apolipoprotein E mimetics, leptin, intranasal insulin, the glucagon-like peptide-1 mimetics and glycogen synthase kinase-3 (GSK-3) antagonists-are all part of an interlocking chain of events. All these approaches inform us that inflammation and thence cerebral insulin resistance constitute the pathway on which to focus for a successful clinical outcome in treating this disease.

Treating primary hypothyroidism with weekly doses of levothyroxine: a randomized, single-blind, crossover study.

Objective: Compliance to levothyroxine treatment in hypothyroidism is compromised by daily schedule, and a weekly dose may be an alternative.

Subjects And Methods: This was a randomized, crossover study. Fourteen females were assigned to daily or weekly doses of LT4.

Effects of leptin deficiency and replacement on cerebellar response to food-related cues.

Leptin affects eating behavior partly by altering the response of the brain to food-related stimuli. The effects of leptin on brain structure have been observed in the cerebellum, where leptin receptors are most densely expressed, but the function of leptin in the cerebellum remains unclear. We performed a nonrandomized, prospective interventional study of three adults with genetically mediated leptin deficiency.