There is overwhelming evidence showing that human activities have contributed to global warming over the past century. Global warming has a severe impact on food and water supplies, housing and other ...infrastructure, health, and economic activities. The human body has thermoregulatory mechanisms that adapt to ambient temperature and maintain normal core body temperature for physiological functions. Here, Ahima discusses how extreme temperatures driven by global warming disrupt normal thermoregulation and imperil human health and survival.
Abstract Leptin is secreted by adipose tissue and regulates energy homeostasis, neuroendocrine function, metabolism, immune function and other systems through its effects on the central nervous ...system and peripheral tissues. Leptin administration has been shown to restore metabolic and neuroendocrine abnormalities in individuals with leptin-deficient states, including hypothalamic amenorrhea and lipoatrophy. In contrast, obese individuals are resistant to leptin. Recombinant leptin is beneficial in patients with congenital leptin deficiency or generalized lipodystrophy. However, further research on molecular mediators of leptin resistance is needed for the development of targeted leptin sensitizing therapies for obesity and related metabolic diseases.
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., α‐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–pituitary–adrenal 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.
Obesity has increased worldwide; is a major risk factor for diabetes, cardiovascular disease, cancer, sleep apnea, nonalcoholic fatty liver disease, osteoarthritis, and other ailments; and has been ...associated with disability, mortality, and enormous health costs (1, 2). Despite these clear adverse consequences of obesity, some studies have suggested that obesity as defined by body mass index (BMI) improves survival under certain conditions (3-8). Here, we discuss the controversies surrounding the "obesity-mortality paradox" and offer potential mechanisms to explain the effects of obesity on health.
Cytosolic lipid droplets (LDs) are present in most cell types, and consist of a core comprising neutral lipids, mainly triglycerides and sterol esters, surrounded by a monolayer of phospholipids. LDs ...are heterogeneous in their structure, chemical composition, and tissue distribution. LDs are coated by several proteins, including perilipins and other structural proteins, lipogenic enzymes, lipases and membrane-trafficking proteins. Five proteins of the perilipin (PLIN) family (PLIN1 (perilipin), PLIN2 (adipose differentiation-related protein), PLIN3 (tail-interacting protein of 47kDa), PLIN4 (S3-12), and PLIN5 (myocardial lipid droplet protein)), are associated with LD formation. More recently, the CIDE family of proteins, hypoxia-inducible protein 2 (HIG2), and patanin-like phospholipase domain-containing 3 (PNPLA3) have also gained attention in hepatic LD biology. Evidence suggests that LD proteins are involved in the pathophysiology of fatty liver diseases characterized by excessive lipid accumulation in hepatocytes. This review article will focus on how hepatic LDs and their associated proteins are involved in the pathogenesis of three chronic liver conditions: hepatitis C virus infection, non-alcoholic fatty liver disease, and alcoholic liver disease.
•We review the major perilipin and non-perilipin hepatic lipid droplet proteins.•We review theoretical models of hepatic lipid droplet formation.•We discuss the role of lipid droplet proteins in HCV, NAFLD, and ALD.
Ayekoo! - Well done Ahima, Rexford S
The Journal of clinical investigation,
02/2022, Letnik:
132, Številka:
3
Journal Article
Recenzirano
Odprti dostop
As the curtain draws on the 5-year term of the JCI editorial board at Johns Hopkins, I am filled with gratitude and would like to extend a warm ayekoo (Ghanaian salutation meaning "well done") to our ...editors, staff, reviewers, and scientists for supporting the Journal. I am delighted to welcome the next JCI Editor in Chief, Elizabeth McNally - the first woman to lead the JCI since it was founded almost a century ago - and her team from Northwestern University.
Digging deeper into obesity Ahima, Rexford S
The Journal of clinical investigation
121, Številka:
6
Journal Article
Recenzirano
Odprti dostop
The growing problem of obesity is associated with multiple morbidities, including increased risk of diabetes, hypertension, heart disease, sleep apnea, and cancer. Obesity promotes disability, ...decreases productivity, and shortens life span. Although much attention has been focused on diet and exercise, these strategies alone are not effective in preventing obesity and maintaining weight loss. Moreover, the development of pharmacological approaches for obesity treatment has been dogged by poor efficacy and serious side effects. The biology of obesity is very complex, and mechanisms linking obesity to various diseases are poorly understood. This issue of the JCI highlights important concepts in our understanding of the pathogenesis of obesity and its complications.
Perilipin 2 (Plin2) is a lipid droplet protein that has roles in both lipid and glucose homeostasis. An increase in Plin2 in liver is associated with the development of steatosis, glucose ...intolerance, and ceramide accumulation in alcoholic liver disease. We investigated the role of Plin2 on energy balance and glucose and lipid homeostasis in wildtype and Plin2 knockout (Plin2KO) mice chronically fed a Lieber-DeCarli liquid ethanol or control diet for six weeks.
We performed in vivo measurements of energy intake and expenditure; body composition; and glucose tolerance. After sacrifice, liver was dissected for histology and lipid analysis.
We found that neither genotype nor diet had a significant effect on final weight, body composition, or energy intake between WT and Plin2KO mice fed alcohol or control diets. Additionally, alcohol feeding did not affect oxygen consumption or carbon dioxide production in Plin2KO mice. We performed glucose tolerance testing and observed that alcohol feeding failed to impair glucose tolerance in Plin2KO mice. Most notably, absence of Plin2 prevented hepatic steatosis and ceramide accumulation in alcohol-fed mice. These changes were related to downregulation of genes involved in lipogenesis and triglyceride synthesis.
Plin2KO mice chronically fed alcohol are protected from hepatic steatosis, glucose intolerance, and hepatic ceramide accumulation, suggesting a critical pathogenic role of Plin2 in experimental alcoholic liver disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Considerable overlap has been identified in the risk factors, comorbidities and putative pathophysiological mechanisms of Alzheimer disease and related dementias (ADRDs) and type 2 diabetes mellitus ...(T2DM), two of the most pressing epidemics of our time. Much is known about the biology of each condition, but whether T2DM and ADRDs are parallel phenomena arising from coincidental roots in ageing or synergistic diseases linked by vicious pathophysiological cycles remains unclear. Insulin resistance is a core feature of T2DM and is emerging as a potentially important feature of ADRDs. Here, we review key observations and experimental data on insulin signalling in the brain, highlighting its actions in neurons and glia. In addition, we define the concept of 'brain insulin resistance' and review the growing, although still inconsistent, literature concerning cognitive impairment and neuropathological abnormalities in T2DM, obesity and insulin resistance. Lastly, we review evidence of intrinsic brain insulin resistance in ADRDs. By expanding our understanding of the overlapping mechanisms of these conditions, we hope to accelerate the rational development of preventive, disease-modifying and symptomatic treatments for cognitive dysfunction in T2DM and ADRDs alike.
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