Kang Yu

Age-associated obesity and muscle atrophy (sarcopenia) are intimately connected and are reciprocally regulated by adipose tissue and skeletal muscle dysfunction. During ageing, adipose inflammation leads to the redistribution of fat to the intra-abdominal area (visceral fat) and fatty infiltrations in skeletal muscles, resulting in decreased overall strength and functionality. Lipids and their derivatives accumulate both within and between muscle cells, inducing mitochondrial dysfunction, disturbing β-oxidation of fatty acids, and enhancing reactive oxygen species (ROS) production, leading to lipotoxicity and insulin resistance, as well as enhanced secretion of some pro-inflammatory cytokines. In turn, these muscle-secreted cytokines may exacerbate adipose tissue atrophy, support chronic low-grade inflammation, and establish a vicious cycle of local hyperlipidaemia, insulin resistance, and inflammation that spreads systemically, thus promoting the development of sarcopenic obesity (SO). We call this the metabaging cycle. Patients with SO show an increased risk of systemic insulin resistance, systemic inflammation, associated chronic diseases, and the subsequent progression to full-blown sarcopenia and even cachexia. Meanwhile in many cardiometabolic diseases, the ostensibly protective effect of obesity in extremely elderly subjects, also known as the 'obesity paradox', could possibly be explained by our theory that many elderly subjects with normal body mass index might actually harbour SO to various degrees, before it progresses to full-blown severe sarcopenia. Our review outlines current knowledge concerning the possible chain of causation between sarcopenia and obesity, proposes a solution to the obesity paradox, and the role of fat mass in ageing.

TarFisDock is a web-based tool for automating the procedure of searching for small molecule-protein interactions over a large repertoire of protein structures. It offers PDTD (potential drug target database), a target database containing 698 protein structures covering 15 therapeutic areas and a reverse ligand-protein docking program. In contrast to conventional ligand-protein docking, reverse ligand-protein docking aims to seek potential protein targets by screening an appropriate protein database. The input file of this web server is the small molecule to be tested, in standard mol2 format; TarFisDock then searches for possible binding proteins for the given small molecule by use of a docking approach. The ligand-protein interaction energy terms of the program DOCK are adopted for ranking the proteins. To test the reliability of the TarFisDock server, we searched the PDTD for putative binding proteins for vitamin E and 4H-tamoxifen. The top 2 and 10% candidates of vitamin E binding proteins identified by TarFisDock respectively cover 30 and 50% of reported targets verified or implicated by experiments; and 30 and 50% of experimentally confirmed targets for 4H-tamoxifen appear amongst the top 2 and 5% of the TarFisDock predicted candidates, respectively. Therefore, TarFisDock may be a useful tool for target identification, mechanism study of old drugs and probes discovered from natural products. TarFisDock and PDTD are available at http://www.dddc.ac.cn/tarfisdock/.

BACKGROUND: Ageing, chronic diseases, prolonged inactivity, and inadequate nutrition pose a severe threat to skeletal muscle health and function. To date, experimental evidence suggests that ageing-related subclinical inflammation could be an important causative factor in sarcopenia. Although inflammatory signalling has been implicated in the pathogenesis of experimental animal models of sarcopenia, few studies have surveyed the clinical association between circulating factors and muscle mass in patients before and after lifestyle interventions. In this study, we evaluated whether proinflammatory cytokines are associated with the onset of sarcopenia, which circulating factors are associated with the severity of sarcopenia, and how these factors change after lifestyle interventions in sarcopenic elderly persons. METHODS: A total of 56 elderly subjects (age ≥ 60 years) with sarcopenia and 56 elderly non-sarcopenic subjects, who met entry criteria and had given informed consent, were selected from the Peking Union Medical College Hospital multicentre prospective longitudinal sarcopenia study for testing relevant circulating factors. Thirty-two elderly subjects from the sarcopenic cohort completed a 12 week intensive lifestyle intervention programme with whey supplements (30 g/day) and a personalized resistance training regimen. The levels of proinflammatory cytokines and metabolic hormones, pre-intensive and post-intensive lifestyle interventions, were measured. RESULTS: The sarcopenic group was significantly older (72.05 ± 6.54 years; P < 0.001), more likely to be inactive and female (57.1% of all sarcopenic patients), and had a higher prevalence of type 2 diabetes (16% higher risk). Compared with non-sarcopenic subjects, serum interleukin (IL)-6, IL-18, tumour necrosis factor-α (TNF-α), TNF-like weak inducer of apoptosis (TWEAK), and leptin were significantly higher, while insulin growth factor 1, insulin, and adiponectin were significantly lower in sarcopenic patients (all P < 0.05). Logistic regression analyses revealed that high levels of TNF-α (>11.15 pg/mL) and TWEAK (>1276.48 pg/mL) were associated with a 7.6-fold and 14.3-fold increased risk of sarcopenia, respectively. After adjustment for confounding variables, high levels of TWEAK were still associated with a 13.4-fold increased risk of sarcopenia. Intensive lifestyle interventions led to significant improvements in sarcopenic patients' muscle mass and serum profiles of TWEAK, TNF-α, IL-18, insulin, and adiponectin (all P < 0.05). CONCLUSIONS: High levels of the inflammatory cytokines TWEAK and TNF-α are associated with an increased risk of sarcopenia, while the metabolic hormones insulin growth factor 1, insulin, and adiponectin are associated with a decreased risk of sarcopenia in our Chinese patient cohort. Intensive lifestyle interventions could significantly improve muscle mass, reduce inflammation, and restore metabolic hormone levels in sarcopenic patients. This trial was registered at clinicaltrials.gov as NCT02873676.

Dietary fibre plays an important role in controlling postprandial glycemic and insulin response in diabetic patients. The intake of dietary fibre has been shown to delay the gastric emptying in healthy subjects. The relationship between gastric emptying and postprandial blood glucose in diabetic patients with fibre-load liquids needs to be investigated. To investigate the impact of soluble dietary fibre (SDF) on gastric emptying, postprandial glycemic and insulin response in patients with type 2 diabetes. 30 patients with type 2 diabetes (DM) and 10 healthy subjects (HS) matched for gender and age were randomized to receive SDF-free liquid (500 mL, 500 Kcal) and isoenergetic SDF liquid (oat β-glucan 7.5 g, 500 mL, 500 Kcal) on two separate days based on a cross-over with 6-day wash-out period. Gastric emptying was monitored by ultrasonography at intervals of 30 min for 2 hours. Fasting and postprandial blood was collected at intervals of 30-60 min for 180 min to determine plasma glucose and insulin. Proximal gastric emptying was delayed by SDF-treatment both in DM (p=0.001) and HS (p=0.037). SDF resulted in less output volume in the distal stomach in DM (p<0.05). SDF decreased postprandial glucose (p=0.001) and insulin (p=0.001) in DM subjects. Postprandial glucose (r=-0.547, p=0.047) and insulin (r=-0.566, p=0.004) were negatively correlated with distal emptying of SDF in DM subjects. Distal gastric emptying was delayed significantly in DM subjects with HbA1c levels ≥6.5% (p=0.021) or with complications (p=0.011) by SDF, respectively. SDF improved postprandial glycaemia which was related to slowing of gastric emptying.