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Leptin was initially best known for its role in energy homeostasis and regulation of energy expenditure. In the past few years we have realized that leptin also plays a major role in neuroendocrine regulation and bone metabolism. Here, we review the literature on indirect and direct pathways through which leptin acts to influence bone metabolism and discuss bone abnormalities related to leptin deficiency in both animal and human studies. The clinical utility of leptin in leptin deficient individuals and its potential to improve metabolic bone disease are also discussed. We are beginning to understand the critical role leptin plays in bone metabolism; future randomized studies are needed to fully assess the potential and risk – benefit of leptin's use in metabolic bone disease particularly in leptin deficient individuals.

Objective To test the hypothesis that autoantigen modifications by peptidylarginine deiminase type 4 (PAD-4) increase immunoreactivity. Methods We assembled sera from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Felty’s syndrome (FS), and antineutrophil cytoplasmic antibody–associated vasculitides (AAVs), as well as sera from control subjects without autoimmune diseases. The sera were tested for binding to activated neutrophils, deiminated histones, and neutrophil extracellular chromatin traps (NETs). IgG binding to lipopolysaccharide-activated neutrophils was assessed with confocal microscopy, and binding to in vitro–deiminated histones was measured using enzyme-linked immunosorbent assay (ELISA) and Western blotting. In addition, we quantitated histone deimination in freshly isolated neutrophils from the blood of patients and control subjects. Results Increased IgG reactivity with activated neutrophils, particularly binding to NETs, was paralleled by preferential binding to deiminated histones over nondeiminated histones by ELISA in a majority of sera from FS patients but only in a minority of sera from SLE and RA patients. Immunoblotting revealed autoantibody preference for deiminated histones H3, H4, and H2A in most FS patients and in a subset of SLE and RA patients. In patients with AAVs, serum IgG preferentially bound nondeiminated histones over deiminated histones. Increased levels of deiminated histones were detected in neutrophils from RA patients. Conclusion Circulating autoantibodies in FS are preferentially directed against PAD-4–deiminated histones and bind to activated neutrophils and NETs. Thus, increased reactivity with modified autoantigens in FS implies a direct contribution of neutrophil activation and the production of NET-associated nuclear autoantigens in the initiation or progression of FS.

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Metabolic syndrome is a cluster of cardiovascular risk factors defined by the presence of abdominal obesity, glucose intolerance, hypertension and/or dyslipidemia. It is a major public health epidemic worldwide, and a known risk factor for the development of cognitive dysfunction and dementia. Several studies have demonstrated a positive association between the presence of metabolic syndrome and worse cognitive outcomes, however, evidence of brain structure pathology is limited. Diffusion tensor imaging has offered new opportunities to detect microstructural white matter changes in metabolic syndrome, and a possibility to detect associations between functional and structural abnormalities. This review analyzes the impact of metabolic syndrome on white matter microstructural integrity, brain structure abnormalities and their relationship to cognitive function. Each of the metabolic syndrome components exerts a specific signature of white matter microstructural abnormalities. Metabolic syndrome and its components exert both additive/synergistic, as well as, independent effects on brain microstructure thus accelerating brain aging and cognitive decline.

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Lorcaserin is a serotonin 5-hydroxytryptamine 2c receptor agonist effective in treating obesity. Studies in rodents have shown that lorcaserin acts in the brain to exert its weight-reducing effects, but this has not yet been studied in humans. We performed a randomized, placebo-controlled, double-blind trial with 48 obese participants and used functional MRI to study the effects of lorcaserin on the brain. Subjects taking lorcaserin had decreased brain activations in the attention-related parietal and visual cortices in response to highly palatable food cues at 1 week in the fasting state and in the parietal cortex in response to any food cues at 4 weeks in the fed state. Decreases in emotion- and salience-related limbic activity, including the insula and amygdala, were attenuated at 4 weeks. Decreases in caloric intake, weight, and BMI correlated with activations in the amygdala, parietal, and visual cortices at baseline. These data suggest that lorcaserin exerts its weight-reducing effects by decreasing attention-related brain activations to food cues (parietal and visual cortices) and emotional and limbic activity (insula, amygdala). Results indicating that baseline activation of the amygdala relates to increased efficacy suggest that lorcaserin would be of particular benefit to emotional eaters.

Infections of the adrenal glands remain an important cause of adrenal insufficiency, especially in the developing world. Indeed, when Thomas Addison first described the condition that now bears his name over 150 years ago, the vast majority of cases were attributable to tuberculosis. Here we describe a classic, but relatively uncommon, presentation in the United States of adrenal insufficiency followed by a review of the current literature pertaining to adrenal infections.