Astaxanthin Ameliorates Worsened Muscle Dysfunction of MDX Mice Fed with a High-Fat Diet through Reducing Lipotoxicity and Regulating Gut Microbiota.

Duchenne muscular dystrophy (DMD), a severe X-linked inherited neuromuscular disease, has a high prevalence of obesity. Obesity exacerbates muscle damage and results in adverse clinical outcomes. Preventing obesity helps DMD patients delay disease progression and improve quality of life. Astaxanthin (AX) is a kind of carotenoid which has antioxidant and anti-adipogenesis effects. In this study, male C57BL/10ScSnDmdmdx/J mice were fed with a normal diet, a high-fat diet (HFD), and an HFD containing AX for 16 weeks, respectively. The results showed that AX significantly increased gastrocnemius fiber cross-section area and grip strength, improved treadmill endurance test and mitochondrial morphology, and reduced muscle triglyceride and malonaldehyde levels compared to the HFD. Lipidomic analysis revealed that AX decreased high levels of triglyceride, diglyceride, ceramides, and wax ester induced by HFD. Gut microbiota analysis indicated that AX supplementation failed to alleviate abnormal microbiota diversity, but increased the relative abundances of Akkermansia, Bifidobacterium, Butyricicoccus, and Staphylococcus. In conclusion, AX was expected to alleviate disease progression associated with obesity in DMD patients by reducing lipotoxicity and increasing the abundance of beneficial bacteria.

Effects of Whey Protein or Its Hydrolysate Supplements Combined with an Energy-Restricted Diet on Weight Loss: A Randomized Controlled Trial in Older Women.

An energy-restricted weight-loss approach has limitations when it used in the elderly, especially because of muscle loss. We aimed to assess the effects of whey protein (WP) or WP hydrolysate (WPH) combined with an energy-restricted diet (ERD) on weight reduction and muscle preservation in older women with overweight and obesity. A total of 60 women were randomized to the control (ERD), WP (ERD + 20 g/d WP) or WPH (ERD + 20 g/d WPH) group, using a 1:1:1 allocation ratio. After an 8-week intervention, body composition, gut microbiota, and serum metabolomics changes were compared among the three groups. The reductions in body weight (−1.11 ± 1.11 vs. −2.34 ± 1.35, p < 0.05), BMI (−0.46 ± 0.45 vs. −0.97 ± 0.54, p < 0.05), and body fat (−0.70 ± 0.92 vs. −2.45 ± 1.65, p < 0.01) were higher in the WPH group than in the control group. Body fat (%) was significantly decreased in the two protein groups. Fat-free mass did not significantly change among the three groups. Serum metabolomics showed that the tricarboxylic acid cycle pathway was upregulated in the WPH group. No significant changes in microbiota were observed among the groups. In conclusion, WP or WPH supplementation combined with an energy-restricted diet benefits older women during weight loss. WPH was more effective, possibly due to increased energy metabolism.

Lactoferrin promotes bile acid metabolism and reduces hepatic cholesterol deposition by inhibiting the farnesoid X receptor (FXR)-mediated enterohepatic axis.

BACKGROUND: Lactoferrin (LF) is a multifunctional glycoprotein that can regulate lipid metabolism, lower cholesterol, reduce body weight, and prevent atherosclerosis. Bile acid (BA) metabolism plays an important role in removing excess cholesterol from the body. However, studies on the effects of LF on BA metabolism are limited and inconsistent. METHODS: Male C57BL/6J mice aged 6-8 weeks were fed with a normal diet (control group), high-fat/high-cholesterol diet containing cholate (HFCCD group), or HFCCD and 1.0% LF in drinking water (LF group) for 8 weeks. Serum and hepatic lipid profiles, and glucose tolerance were measured. Fecal BA composition was determined through ultra-high performance liquid chromatography-tandem mass spectrometry. The gene expression of BA synthase in the liver and farnesoid X receptor (FXR)-mediated BA negative feedback regulation pathway in the liver and ileum were analyzed via RNA analysis. RESULTS: HFCCD resulted in abnormal cholesterol levels in the serum and liver. LF intervention significantly increased the serum high-density lipoprotein cholesterol level by 24.9% and decreased the hepatic total cholesterol content by 26%. LF treatment significantly increased the BA content per gram by 109.8%, the total amount of BA excretion by 153.5% and conjugated BAs by 87.6% in the feces. Furthermore, LF upregulated the expression of the hepatic sterol 12α-hydroxylase (CYP8B1) gene, which expresses important enzymes in the classical pathway of BA synthesis, and the bile acid-CoA amino acid N-acetyltransferase (BAAT) gene, which is responsible for the formation of conjugated BAs. The FXR-mediated pathways in the enterohepatic axis, including FXR, fibroblast growth factor 15, and fibroblast growth factor receptor 4, were inhibited by LF. CONCLUSIONS: LF ameliorated hepatic cholesterol deposition in mice fed with a high-fat and high cholesterol diet containing cholate. LF elevated the conjugated BA level, inhibited the ileum FXR and FXR-mediated enterohepatic axis, and increased BA synthesis and excretion.

Fasting blood glucose levels and prognosis in patients with non-small-cell lung cancer: a prospective cohort study in China.

PURPOSE: Non-small-cell lung cancer (NSCLC) is the most diagnosed lung cancer and is associated with poor prognosis. This study aimed to analyze whether fasting blood glucose (FBG) levels could provide prognostic information in Chinese patients with NSCLC, using the Suzhou Lung Cancer Survival study. PATIENTS AND METHODS: A prospective cohort study of adult patients with primary NSCLC was performed. The patients who were hospitalized between January 2016 and April 2018 in two hospitals affiliated with Soochow University were recruited. Patient information, including lifestyle habits and clinical and laboratory data, were collected through face-to-face interviews and evaluation of medical records. Follow-up was initiated from the date of patient enrollment until May 8, 2018 or until patient death. The long-term survival of patients was assessed every 6 months. Patient vital status was confirmed by using hospital records, telephone interview, or local death registration system. Cox proportional hazards regression was used to estimate hazard ratio and 95% confidence interval (CI) for death, with adjustment for cancer stage, medical treatments, smoking, and other potential confounders. RESULTS: A total of 387 patients were included in the analysis, and the numbers (percentages) of patients with stages I, II, III, and IV NSCLC were 53 (13.7%), 41 (10.6%), 64 (16.5%), and 215 (55.6%), respectively. The median duration of follow-up was 19.1 months. Compared with patients in the second tertile of FBG, the HRs for mortality were 2.16 (95% CI: 1.26-3.73) and 1.87 (95% CI: 1.03-3.42) for those in the lowest one and diabetic group, respectively. Subgroup analysis according to various patient characteristics confirmed these associations. CONCLUSION: Diabetes and low FBG could be important predictors of death in patients with NSCLC. Maintaining appropriate blood glucose levels may improve prognosis in patients with NSCLC.

Lactoferrin Alleviates the Progression of Atherosclerosis in ApoE-/- Mice Fed with High-Fat/Cholesterol Diet Through Cholesterol Homeostasis.

Lactoferrin (LF) is a multifunctional glycoprotein and has beneficial effects on the regulation of lipid metabolism. However, whether LF supplementation alleviates the development of atherosclerosis (AS) remains unclear. In the present study, all of 48 male Apolipoprotein E-/- mice were fed with high-fat diet with 1.25% added cholesterol and divided to four treatment groups with either distilled water (HFCD), LF solutions at 2 mg/mL (low LF), 10 mg/mL (middle LF or MLF), or 20 mg/mL (high LF or HLF) for 12 weeks. Oral glucose tolerance tests (OGTT) were performed at weeks 0, 4, 8, and 12. At the end of the experiment, lipids in serum, liver, and feces were determined. The livers, whole aortas, and aortic sinuses were pathologically examined. The protein expression of factors related to cholesterol synthesis, absorption, and excretion were detected through western blot. No significant difference in body weight, food intake, and OGTT was observed among the four groups. Compared with the HFCD group, the MLF and HLF groups had significantly decreased serum and hepatic cholesterol levels and significantly increased fecal cholesterol contents. LF alleviated the hepatic steatosis and lipid droplet, especially in the MLF group. LF also significantly decreased the average lesion areas in the whole aorta, especially in the MLF group. On the other hand, LF downregulated hepatic protein expression of HMG-CoA reductase (the rate-limiting enzyme in cholesterol synthesis) and upregulated cholesterol 7-alpha hydroxylase (the rate-limiting enzyme in bile acid synthesis from cholesterol). LF also downregulated the intestinal expression of Niemann-Pick C1-like 1 protein, which is known to bind to a critical mediator of cholesterol absorption. In conclusion, LF supplementation alleviates the AS in mice on HFCD likely by reducing the synthesis and absorption of cholesterol and increasing cholesterol excretion.

Holo-Lactoferrin Modified Liposome for Relieving Tumor Hypoxia and Enhancing Radiochemotherapy of Cancer.

Hypoxic microenvironments in the solid tumor play a negative role in radiotherapy. Holo-lactoferrin (holo-Lf) is a natural protein, which acts as a potential ligand of transferrin receptor (TfR). In this work, an anticancer drug, doxorubicin (Dox)-loaded liposome-holo-Lf nanocomposites, is developed for tumor targeting and imaging guided combined radiochemotherapy. Dox-loaded liposome-holo-Lf (Lf-Liposome-Dox) nanocomposites exhibit significant cellular uptake likely owing to the TfR receptor-mediated targeting accumulation of Lf-Liposome-Dox nanocomposites. Additionally, the nanocomposites exhibit high accumulation in the tumor site after intravenous injection as evidenced from in vivo fluorescence imaging. More importantly, it is found that the holo-Lf has the ability to catalyze the conversion of hydrogen peroxide (H2 O2 ) to oxygen for relieving the tumor hypoxic microenvironment. Photoacoustic imaging further confirms the abundant generation of oxygen in the presence of Lf-Liposome-Dox nanocomposites. Based on these findings, in vivo combined radiochemotherapy is performed using Lf-Liposome-Dox as therapeutic agent, achieving excellent cancer treatment effect. The study further promotes the potential biomedical application of holo-Lf in cancer treatment.