Adipose tissue as an endocrine organ,”

Abstract AHIMA, REXFORD S. Adipose tissue as an endocrine organ. Obesity. 2006;14(Suppl 5):242S-249S. Adipose tissue plays a critical role in energy homeostasis, not only in storing triglycerides, but also responding to nutrient, neural, and hormonal signals and secreting adipokines that control feeding, thermogenesis, immunity, and neuroendocrine function. A rise in leptin signals satiety to the brain through receptors in hypothalamic and brainstem neurons. Leptin activates tyrosine kinase, Janus kinase 2, and signal transducer and activator of transcription 3, leading to increased levels of anorexigenic peptides, e.g., ␣-melanocyte stimulating hormone and cocaine-and amphetamine-regulated transcript, and inhibition of orexigenic peptides, e.g., neuropeptide Y and agouti-related peptide. Obesity is characterized by hyperleptinemia and hypothalamic leptin resistance, partly caused by induction of suppressor of cytokine signaling-3. Leptin falls rapidly during fasting and potently stimulates appetite, reduces thermogenesis, and mediates the inhibition of thyroid and reproductive hormones and activation of the hypothalamic-pituitaryadrenal axis. These actions are integrated by the paraventicular hypothalamic nucleus. Leptin also decreases glucose and stimulates lipolysis through central and peripheral pathways involving AMP-activated protein kinase (AMPK). Adiponectin is secreted exclusively by adipocytes and has been linked to glucose, lipid, and cardiovascular regulation. Obesity, diabetes, and atherosclerosis have been associated with reduced adiponectin levels, whereas adiponectin treatment reverses these abnormalities partly through activation of AMPK in liver and muscle. Administration of adiponectin in the brain recapitulates the peripheral actions to increase fatty acid oxidation and insulin sensitivity and reduce glucose. Although putative adiponectin receptors are widespread in peripheral organs and brain, it is uncertain whether adiponectin acts exclusively through these targets. As with leptin, adiponectin requires the central melanocortin pathway. Furthermore, adiponectin stimulates fatty acid oxidation and reduces glucose and lipids, at least in part, by activating AMPK in muscle and liver

Squalamine: An Appropriate Strategy against the Emergence of Multidrug Resistant Gram-Negative Bacteria?

We reported that squalamine is a membrane-active molecule that targets the membrane integrity as demonstrated by the ATP release and dye entry. In this context, its activity may depend on the membrane lipid composition. This molecule shows a preserved activity against bacterial pathogens presenting a noticeable multi-resistance phenotype against antibiotics such as polymyxin B. In this context and because of its structure, action and its relative insensitivity to efflux resistance mechanisms, we have demonstrated that squalamine appears as an alternate way to combat MDR pathogens and by pass the gap regarding the failure of new active antibacterial molecules

Can the Obesity Crisis Be Reversed?

How can we work together to understand the rise of obesity and reverse its related diseases and societal impacts?Obesity is a complex condition that increases a person's risk for developing diabetes, heart disease, cancer, dementia, and other life-threatening conditions. Contrary to prevailing notions that it results solely from a person's diet and exercise failings, a predisposition to obesity is actually determined by genetics as well as by environmental and socioeconomic factors that lie beyond individual control. In Can the Obesity Crisis Be Reversed?, Dr. Rexford Ahima draws on his extensive laboratory and clinical experiences at top institutions to examine the complicated causes of obesity, as well as the most cutting-edge approaches for prevention and treatment. Ahima looks at how the rising trends of obesity and associated diseases are driving up health care costs. He also offers insight into the widespread suffering that obesity imposes and its disproportionate impacts in minority and underserved communities.Calling for greater societal and community engagement in stemming the obesity crisis, Ahima argues that there is an urgent need to promote healthier foods and environmental infrastructure as well as formal programs that reduce obesity. By understanding and applying fundamental knowledge, Can the Obesity Crisis Be Reversed? makes a convincing case that all of us, working individually and collectively, can help to reverse the obesity crisis.Features• Provides information on the biological pathways that control eating and metabolism• Explains genetic and environmental bases of obesity• Reviews the contributions of diet and physical activity to weight gain while speaking to the folly and dangers of individual blame• Offers practical recommendations for healthy diets, exercise, and lifestyle• Discusses current medical and surgical treatments of obesity• Examines comprehensive societal strategies for obesity preventionJohns Hopkins WavelengthsIn classrooms, field stations, and laboratories in Baltimore and around the world, the Bloomberg Distinguished Professors of Johns Hopkins University are opening the boundaries of our understanding of many of the world's most complex challenges. The Johns Hopkins Wavelengths book series brings readers inside their stories, illustrating how their pioneering discoveries benefit people in their neighborhoods and across the globe in artificial intelligence, cancer research, food systems' environmental impacts, health equity, science diplomacy, and other critical arenas of study. Through these compelling narratives, their insights will spark conversations from dorm rooms to dining rooms to boardrooms

Resistin in Rodents and Humans

Obesity is characterized by excess accumulation of lipids in adipose tissue and other organs, and chronic inflammation associated with insulin resistance and an increased risk of type 2 diabetes. Obesity, type 2 diabetes, and cardiovascular diseases are major health concerns. Resistin was first discovered as an adipose-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents. Adipocyte-derived resistin is increased in obese rodents and strongly related to insulin resistance. However, in contrast to rodents, resistin is expressed and secreted from macrophages in humans and is increased in inflammatory conditions. Some studies have also suggested an association between increased resistin levels and insulin resistance, diabetes and cardiovascular disease. Genetic studies have provided additional evidence for a role of resistin in insulin resistance and inflammation. Resistin appears to mediate the pathogenesis of atherosclerosis by promoting endothelial dysfunction, vascular smooth muscle cell proliferation, arterial inflammation, and formation of foam cells. Indeed, resistin is predictive of atherosclerosis and poor clinical outcomes in patients with coronary artery disease and ischemic stroke. There is also growing evidence that elevated resistin is associated with the development of heart failure. This review will focus on the biology of resistin in rodents and humans, and evidence linking resistin with type 2 diabetes, atherosclerosis, and cardiovascular disease

Connecting Myokines and Metabolism

Skeletal muscle is the largest organ of the body in non-obese individuals and is now considered to be an endocrine organ. Hormones (myokines) secreted by skeletal muscle mediate communications between muscle and liver, adipose tissue, brain, and other organs. Myokines affect muscle mass and myofiber switching, and have profound effects on glucose and lipid metabolism and inflammation, thus contributing to energy homeostasis and the pathogenesis of obesity, diabetes, and other diseases. In this review, we summarize recent findings on the biology of myokines and provide an assessment of their potential as therapeutic targets

Body fat predicts exercise capacity in persons with Type 2 Diabetes Mellitus: A machine learning approach.

Diabetes mellitus is associated with increased cardiovascular disease (CVD) related morbidity, mortality and death. Exercise capacity in persons with type 2 diabetes has been shown to be predictive of cardiovascular events. In this study, we used the data from the prospective randomized LOOK AHEAD study and used machine learning algorithms to help predict exercise capacity (measured in Mets) from the baseline data that included cardiovascular history, medications, blood pressure, demographic information, anthropometric and Dual-energy X-Ray Absorptiometry (DXA) measured body composition metrics. We excluded variables with high collinearity and included DXA obtained Subtotal (total minus head) fat percentage and Subtotal lean mass (gms). Thereafter, we used different machine learning methods to predict maximum exercise capacity. The different machine learning models showed a strong predictive performance for both females and males. Our study shows that using baseline data from a large prospective cohort, we can predict maximum exercise capacity in persons with diabetes mellitus. We show that subtotal fat percentage is the most important feature for predicting the exercise capacity for males and females after accounting for other important variables. Until now, BMI and waist circumference were commonly used surrogates for adiposity and there was a relative under-appreciation of body composition metrics for understanding the pathophysiology of CVD. The recognition of body fat percentage as an important marker in determining CVD risk has prognostic implications with respect to cardiovascular morbidity and mortality