Atherogenic low density lipoproteins are cleared from the circulation by hepatic low density lipoprotein receptors (LDLR). Two inherited forms of hypercholesterolemia result from loss of LDLR activity: autosomal dominant familial hypercholesterolemia (FH), caused by mutations in the LDLR gene, and autosomal recessive hypercholesterolemia (ARH), of unknown etiology. Here we map the ARH locus to an approximately 1-centimorgan interval on chromosome 1p35 and identify six mutations in a gene encoding a putative adaptor protein (ARH). ARH contains a phosphotyrosine binding (PTB) domain, which in other proteins binds NPXY motifs in the cytoplasmic tails of cell-surface receptors, including the LDLR. ARH appears to have a tissue-specific role in LDLR function, as it is required in liver but not in fibroblasts.

Patients with chronic kidney disease (CKD) experience substantial loss of muscle mass, weakness and poor physical performance. As kidney disease progresses, skeletal muscle dysfunction forms a common pathway for mobility limitation, loss of functional independence, and vulnerability to disease complications. Screening for those at high-risk of mobility disability by self-reported and objective measures of function is an essential first step in developing an interdisciplinary approach to treatment which includes rehabilitative therapies and counseling on physical activity. Exercise has beneficial effects on systemic inflammation, muscle and physical performance in CKD. Kidney health providers need to identify patient- and care delivery barriers to exercise in order to effectively counsel patients on physical activity. A thorough medical evaluation and assessment of baseline function using self-reported and objective function assessment is essential to guide an effective, individualized exercise prescription to prevent function decline in persons with kidney disease. This review focuses on the impact of kidney disease on skeletal muscle dysfunction in the context of the disablement process and reviews screening and treatment strategies that kidney health professionals can employ in clinical practice to prevent functional decline and disability.

Exercise training (EX) may decrease adipose tissue inflammation, thereby ameliorating such disturbances, even in the absence of fat loss. The purpose of this study was to 1) compare the effects of low-fat diet (LFD), EX, and their combination on inflammation, insulin resistance, and hepatic steatosis in high-fat diet-induced obese mice and 2) determine the effect of intervention duration (i.e., 6 vs. 12 wk). C57BL/6 mice (n ϭ 109) fed a 45% fat diet (HFD) for 6 wk were randomly assigned to an EX (treadmill: 5 days/wk, 6 or 12 wk, 40 min/day, 65-70% V O2max) or sedentary (SED) group. Mice remained on HFD or were placed on a 10% fat diet (LFD) for 6 or 12 wk. Following interventions, fat pads were weighed and expressed relative to body weight; hepatic steatosis was assessed by total liver triglyceride and insulin resistance by HOMA-IR and glucose AUC. RT-PCR was used to determine adipose gene expression of MCP-1, F4/80, TNF-␣, and leptin. By 12 wk, MCP-1, F4/80, and TNF-␣ mRNA were reduced by EX and LFD. Exercise (P ϭ 0.02), adiposity (P ϭ 0.03), and adipose F4/80 (P ϭ 0.02) predicted reductions in HOMA-IR (r 2 ϭ 0.75, P Ͻ 0.001); only adiposity (P ϭ 0.04) predicted improvements in hepatic steatosis (r 2 ϭ 0.51, P Ͻ 0.001). Compared with LFD, EX attenuated increases in adiposity, hepatic steatosis, and adipose MCP-1 expression from 6 to 12 wk. There are unique metabolic consequences of a sedentary lifestyle and HFD that are most evident long term, highlighting the importance of both EX and LFD in preventing obesity-related metabolic disturbances. obesity; insulin resistance; hepatic steatosis; macrophage OBESITY RESULTS FROM AN ENERGY IMBALANCE attributable to our current lifestyle, which includes little physical activity and excessive intake of foods high in saturated and trans fats and refined carbohydrates. Consumption of a high-fat Western diet (HFD) and physical inactivity are potential triggers of chronic diseases such as type 2 diabetes and cardiovascular disease. Insulin resistance (IR) and lipid accumulation in the liver are two common metabolic changes that increase the risk of such chronic diseases. It is now recognized that hepatic steatosis (the initial stage of nonalcoholic fatty liver disease) and insulin resistance should be targeted early to prevent complications associated with these conditions. Visceral white adipose tissue (WAT) is currently believed to be the key depot linked with obesity-related systemic metabolic disturbances (6). WAT becomes inflamed during adipose tissue hypertrophy due to an influx of macrophages (M⌽s) that secrete proinflammatory cytokines, including tumor necrosis factor (TNF)-␣. The cause of M⌽ influx into WAT is not completely understood, but an increase in the gene expression of monocyte chemoattractant protein-1 (MCP-1) in WAT has been shown to precede M⌽ entry, suggesting that this chemokine plays an important role in WAT M⌽ accumulation (15).Attenuating inflammation in WAT beneficially modifies (15) these metabolic disturbances and reduces disease risk, even in th...

These results suggest that endurance exercise training may improve CVD risk in haemodialysis patients by decreasing novel risk factors including serum oxidative stress, ALP and epicardial fat.