Aug 1, 2014
Spectrum of statin hepatotoxicity: Experience of the drug-induced liver injury network
The HMG-CoA reductase inhibitors (statins) are widely prescribed for patients with hyperlipidemia and are generally well tolerated. Mild elevations in serum aminotransferases arise in up to 3% of treated patients, but clinically apparent drug-induced liver injury is rare. The aim of this study is to report the presenting features and outcomes of 22 patients with clinically apparent liver injury due to statins.
Jul 8, 2014
NIH study finds extreme obesity may shorten life expectancy up to 14 years
Adults with extreme obesity have increased risks of dying at a young age from cancer and many other causes including heart disease, stroke, diabetes, and kidney and liver diseases, according to results of an analysis of data pooled from 20 large studies of people from three countries. The study, led by researchers from the National Cancer Institute (NCI), part of the National Institutes of Health, found that people with class III (or extreme) obesity had a dramatic reduction in life expectancy compared with people of normal weight. The findings appeared July 8, 2014, in PLOS Medicine.
Jul 3, 2014
Acute kidney injury, chronic kidney disease each a risk of the other
Acute kidney injury (AKI) and chronic kidney disease (CKD) are closely intertwined, with each disease a risk factor for developing the other and sharing other risk factors in common, as well as sharing causes for the diseases to get worse, and outcomes, suggests a comprehensive analysis by scientists at the National Institutes of Health and George Washington University Medical Center, Washington, D.C. Findings were published July 3 in the New England Journal of Medicine.
Jul 2, 2014
Gene type confers 26 percent chance of early celiac sign by age 5
More than one quarter of children with two copies of a high-risk variant in a specific group of genes develop an early sign of celiac disease called celiac disease autoimmunity (CDA) by age 5. The findings are from The Environmental Determinants of Diabetes in Youth consortium, or TEDDY . The National Institutes of Health-funded study, published July 2 in the New England Journal of Medicine , also found that participants in Sweden had higher rates of celiac disease than participants in the United States, Finland and Germany, even with the same genetic risks.
Jul 1, 2014
Myosin Vb uncoupling from RAB8A and RAB11A elicits microvillus inclusion disease
Microvillus inclusion disease (MVID) is a severe form of congenital diarrhea that arises from inactivating mutations in the gene encoding myosin Vb (MYO5B). We have examined the association of mutations in MYO5B and disruption of microvillar assembly and polarity in enterocytes. Stable MYO5B knockdown (MYO5B-KD) in CaCo2-BBE cells elicited loss of microvilli, alterations in junctional claudins, and disruption of apical and basolateral trafficking; however, no microvillus inclusions were observed in MYO5B-KD cells.
Jul 1, 2014
Adults stop anti-rejection drugs after partial stem-cell transplant reverses sickle cell disease
Half of patients in a trial have safely stopped immunosuppressant medication following a modified blood stem-cell transplant for severe sickle cell disease, according to a study in the July 1 issue of the Journal of the American Medical Association. The trial was conducted at the National Institutes of Health’s Clinical Center in Bethesda, Maryland, by researchers from NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Heart, Lung, and Blood Institute.
Jun 30, 2014
NIH-funded researchers extend liver preservation for transplantation
Researchers have developed a new supercooling technique to increase the amount of time human organs could remain viable outside the body. This study was conducted in rats, and if it succeeds in humans, it would enable a world-wide allocation of donor organs, saving more lives.
Jun 19, 2014
The Diabetes Susceptibility Gene Clec16a Regulates Mitophagy
Clec16a has been identified as a disease susceptibility gene for type 1 diabetes, multiple sclerosis, and adrenal dysfunction, but its function is unknown. Here we report that Clec16a is a membrane-associated endosomal protein that interacts with E3 ubiquitin ligase Nrdp1. Loss of Clec16a leads to an increase in the Nrdp1 target Parkin, a master regulator of mitophagy. Islets from mice with pancreas-specific deletion of Clec16a have abnormal mitochondria with reduced oxygen consumption and ATP concentration, both of which are required for normal β cell function.
Jun 17, 2014
α-Intercalated cells defend the urinary system from bacterial infection
α-Intercalated cells (A-ICs) within the collecting duct of the kidney are critical for acid-base homeostasis. Here, we have shown that A-ICs also serve as both sentinels and effectors in the defense against urinary infections. In a murine urinary tract infection model, A-ICs bound uropathogenic E. coli and responded by acidifying the urine and secreting the bacteriostatic protein lipocalin 2 (LCN2; also known as NGAL). A-IC-dependent LCN2 secretion required TLR4, as mice expressing an LPS-insensitive form of TLR4 expressed reduced levels of LCN2.
Jun 15, 2014
Bionic pancreas outperforms insulin pump in adults, youth
People with type 1 diabetes who used a bionic pancreas instead of manually monitoring glucose using fingerstick tests and delivering insulin using a pump were more likely to have blood glucose levels consistently within the normal range, with fewer dangerous lows or highs. The full report of the findings, funded by the National Institutes of Health, can be found online June 15 in the New England Journal of Medicine.
Jun 10, 2014
More than 29 million Americans have diabetes; 1 in 4 doesn’t know
More than 29 million people in the United States have diabetes, up from the previous estimate of 26 million in 2010, according to a report released today by the Centers for Disease Control and Prevention. One in four people with diabetes doesn’t know he or she has it.
Jun 5, 2014
Meteorin-like Is a Hormone that Regulates Immune-Adipose Interactions to Increase Beige Fat Thermogenesis
Exercise training benefits many organ systems and offers protection against metabolic disorders such as obesity and diabetes. Using the recently identified isoform of PGC1-α (PGC1-α4) as a discovery tool, we report the identification of meteorin-like (Metrnl), a circulating factor that is induced in muscle after exercise and in adipose tissue upon cold exposure. Increasing circulating levels of Metrnl stimulates energy expenditure and improves glucose tolerance and the expression of genes associated with beige fat thermogenesis and anti-inflammatory cytokines.
Jun 5, 2014
Eosinophils and Type 2 Cytokine Signaling in Macrophages Orchestrate Development of Functional Beige Fat
Beige fat, which expresses the thermogenic protein UCP1, provides a defense against cold and obesity. Although a cold environment is the physiologic stimulus for inducing beige fat in mice and humans, the events that lead from the sensing of cold to the development of beige fat remain poorly understood. Here, we identify the efferent beige fat thermogenic circuit, consisting of eosinophils, type 2 cytokines interleukin (IL)-4/13, and alternatively activated macrophages. Genetic loss of eosinophils or IL-4/13 signaling impairs cold-induced biogenesis of beige fat.
Jun 5, 2014
Eosinophils in Fat: Pink is the New Brown
Subcutaneous white adipose tissue can be induced to undergo “browning” and acquire thermogenic capacity in response to physiological stimuli such as cold exposure or exercise. In this issue of Cell, Qiu et al. and Rao et al. demonstrate that pink-staining eosinophils and alternatively activated macrophages play key roles in an immune cascade mediating this metabolic switch.
May 21, 2014
Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase.
Metformin is considered to be one of the most effective therapeutics for treating type 2 diabetes because it specifically reduces hepatic gluconeogenesis without increasing insulin secretion, inducing weight gain or posing a risk of hypoglycaemia1, 2. For over half a century, this agent has been prescribed to patients with type 2 diabetes worldwide, yet the underlying mechanism by which metformin inhibits hepatic gluconeogenesis remains unknown.
May 21, 2014
Null Mutation in Hormone-Sensitive Lipase Gene and Risk of Type 2 Diabetes
Lipolysis regulates energy homeostasis through the hydrolysis of intracellular triglycerides and the release of fatty acids for use as energy substrates or lipid mediators in cellular processes. Genes encoding proteins that regulate energy homeostasis through lipolysis are thus likely to play an important role in determining susceptibility to metabolic disorders.
May 6, 2014
Chloride sensing by WNK1 involves inhibition of autophosphorylation
WNK1 [with no lysine (K)] is a serine-threonine kinase associated with a form of familial hypertension. WNK1 is at the top of a kinase cascade, leading to phosphorylation of several cotransporters, in particular those transporting sodium, potassium, and chloride (NKCC), sodium and chloride (NCC), and potassium and chloride (KCC). The responsiveness of NKCC, NCC, and KCC to changes in extracellular chloride parallels their phosphorylation state, provoking the proposal that these transporters are controlled by a chloride-sensitive protein kinase.
May 6, 2014
Opiorphin is a master regulator of the hypoxic response in corporal smooth muscle cells
Men with sickle cell disease (SCD) risk developing priapism. Recognizing that SCD is a disease of hypoxia, we investigated the effect of hypoxia on gene expression in corporal smooth muscle (CSM) cells. Rat CSM cells in vitro were treated with CoCl2 or low oxygen tension to mimic hypoxia. Hypoxic conditions increased expression of genes previously associated with priapism in animal models.
May 4, 2014
Persistent gut microbiota immaturity in malnourished Bangladeshi children
Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM), but incomplete restoration of healthy growth remains a major problem1, 2. The relationships between the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S ribosomal RNA data sets generated from monthly faecal samples obtained from birth onwards in a cohort of children living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth.
May 4, 2014
Drug pair cuts children's urinary infections up to 80 percent
Long-term use of a drug combination reduces the risk of recurrent urinary tract infection by up to 80 percent in children with the urinary condition vesicoureteral compared to placebo, according to research funded by the National Institutes of Health. Results were published online May 4 in theNew England Journal of Medicine External Web Site Policy to coincide with presentation at the Pediatric Academic Societies Annual Meeting in Vancouver, British Columbia.
May 3, 2014
Steroids after surgery do not help infants with rare liver disease
Infants with biliary atresia — a rare liver disease — did not benefit from corticosteroid treatment after bile duct surgery and could face more harm, according to a study funded by the National Institutes of Health. Results were published online May 3 in the Journal of the American Medical Association to coincide with the Pediatric Academic Societies annual meeting.
Apr 1, 2014
PPARγ in Vagal Neurons Regulates High-Fat Diet Induced Thermogenesis
The vagus nerve innervates visceral organs providing a link between key metabolic cues and the CNS. However, it is not clear whether vagal neurons can directly respond to changing lipid levels and whether altered “lipid sensing” by the vagus nerve regulates energy balance. In this study, we systematically profiled the expression of all known nuclear receptors in laser-captured nodose ganglion (NG) neurons. In particular, we found PPARγ expression was reduced by high-fat-diet feeding. Deletion of PPARγ in Phox2b neurons promoted HFD-induced thermogenesis that involved the reprograming of white adipocyte into a brown-like adipocyte cell fate.
Mar 20, 2014
The number of fetal nephron progenitor cells limits ureteric branching and adult nephron endowment
Nephrons, the functional units of the kidney, develop from progenitor cells (cap mesenchyme [CM]) surrounding the epithelial ureteric bud (UB) tips. Reciprocal signaling between UB and CM induces nephrogenesis and UB branching. Although low nephron number is implicated in hypertension and renal disease, the mechanisms that determine nephron number are obscure. To test the importance of nephron progenitor cell number, we genetically ablated 40% of these cells, asking whether this would limit kidney size and nephron number or whether compensatory mechanisms would allow the developing organ to recover.
Mar 13, 2014
NIH urges older Americans to protect their kidneys
In recognition of World Kidney Day 2014 on March 13, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institute on Aging (NIA) at the National Institutes of Health remind older Americans about the importance of protecting their kidneys and urge them to better understand the decline of kidney function as people age.
Feb 14, 2014
Risk of end-stage renal disease following live kidney donation
Risk of end-stage renal disease (ESRD) in kidney donors has been compared with risk faced by the general population, but the general population represents an unscreened, high-risk comparator. A comparison to similarly screened healthy nondonors would more properly estimate the sequelae of kidney donation.
Jan 30, 2014
Nonstochastic reprogramming from a privileged somatic cell state
Reprogramming somatic cells to induced pluripotency by Yamanaka factors is usually slow and inefficient and is thought to be a stochastic process. We identified a privileged somatic cell state, from which acquisition of pluripotency could occur in a nonstochastic manner. Subsets of murine hematopoietic progenitors are privileged whose progeny cells predominantly adopt the pluripotent fate with activation of endogenous Oct4 locus after four to five divisions in reprogramming conditions.
Jan 16, 2014
Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells
Coevolution of beneficial microorganisms with the mammalian intestine fundamentally shapes mammalian physiology. Here, we report that the intestinal microbe Bacteroides fragilis modifies the homeostasis of host invariant natural killer T (iNKT) cells by supplementing the host’s endogenous lipid antigen milieu with unique inhibitory sphingolipids. The process occurs early in life and effectively impedes iNKT cell proliferation during neonatal development.