Journal: CNS Neuroscience & Therapeutics

Article Title: Microbial lipopolysaccharide‐induced inflammation contributes to cognitive impairment and white matter lesion progression in diet‐induced obese mice with chronic cerebral hypoperfusion

doi: 10.1111/cns.14301

Figure Lengend Snippet: High‐fat diet (HFD) feeding alters gut microbiota composition and increases intestinal permeability, plasma lipopolysaccharide (LPS) concentration, and plasma pro‐inflammatory cytokine concentrations in wild‐type mice. (A) Alpha diversity metrics for HFD and low‐fat diet mice, including richness (left), Shannon index (center), and Faith's phylogenetic diversity (right) ( n = 5 per group). (B) Principal coordinate analysis based on weighted UniFrac distances ( n = 5 per group). (C) Relative abundance of bacteria at the genus level ( n = 5 per group). (D) Intestinal permeability ( n = 5 per group). (E) Plasma LPS concentrations ( n = 7 per group). (F) Plasma concentrations of IL‐6 and IL‐1β ( n = 5 per group). Results are presented as median ± interquartile range (A, C) and mean ± SD (D–F). * p < 0.05, ** p < 0.01.

Article Snippet: All mice were maintained on a 12‐h/12‐h light/dark cycle and administered a low‐fat diet (LFD) with 10.2 kcal% fat or an HFD with 56.7 kcal% fat (Japan CLEA Inc.) (Table ) from 5 to 16 weeks of age.

Techniques: Permeability, Clinical Proteomics, Concentration Assay, Bacteria

Journal: Disease Models & Mechanisms

Article Title: Independent effects of dietary fat and sucrose content on chondrocyte metabolism and osteoarthritis pathology in mice

doi: 10.1242/dmm.034827

Figure Lengend Snippet: Effect of diet on body mass and adiposity. (A,B) Increased dietary fat content, but not sucrose, increased body mass (A) and body fat (B). Data were collected at 25 weeks of age after 19 weeks of diet treatment. Body fat, expressed as a percent of total body mass, was measured by dual-energy X-ray absorptiometry (DEXA). Data shown are for one cohort of animals, although values are consistent with data from additional cohorts. Values are mean±s.e.m. Lines over bars indicate statistically significant differences (**** P <0.0001 by one-way ANOVA and Tukey's multiple comparisons test; LFLS, n =10; LFHS, n =8; HFLS, n =10).

Article Snippet: Beginning at 6 weeks of age, animals were fed one of three irradiated, purified open source diets (Research Diets Inc., USA; Table S1 ): (1) low-fat low-sucrose (LFLS) diet containing 10% kcal fat and 7% sucrose (product D12450Ji); (2) low-fat high-sucrose (LFHS) diet containing 10% kcal fat and 35% sucrose (product D12450Bi); or (3) high-fat low-sucrose (HFLS) diet containing 60% kcal fat and 7% sucrose (product D12492i).

Techniques:

Journal: Disease Models & Mechanisms

Article Title: Independent effects of dietary fat and sucrose content on chondrocyte metabolism and osteoarthritis pathology in mice

doi: 10.1242/dmm.034827

Figure Lengend Snippet: Dietary sucrose and fat independently alter serum metabolic biomarkers. Metabolic markers were generally lower in mice fed the LFHS diet compared with those fed the LFLS diet. Consequently, markers were more likely to be significantly elevated in mice fed a HFLS diet when compared with mice fed a low-fat diet that contained more, not less, sucrose. Blood was obtained by terminal cardiac puncture between 09:00 and 11:00 following a 1-2 h fast. Data points are values for individual animals, and horizontal bars are mean±s.e.m. Results that include two LFLS samples excluded due to liver nodules are shown in Fig. S1 . Lines over bars indicate statistically significant differences (* P <0.05, ** P <0.01, *** P <0.001 by one-way ANOVA and Tukey's multiple comparisons test or Kruskal–Wallis test with Dunn's multiple comparisons test; LFLS, n =6-8; LFHS, n =5-6; HFLS, n =4-9). Variations in sample size were due to marker detectability. ALKP, alkaline phosphatase; ALT, alanine aminotransferase; GGT, gamma-glutamyltransferase.

Article Snippet: Beginning at 6 weeks of age, animals were fed one of three irradiated, purified open source diets (Research Diets Inc., USA; Table S1 ): (1) low-fat low-sucrose (LFLS) diet containing 10% kcal fat and 7% sucrose (product D12450Ji); (2) low-fat high-sucrose (LFHS) diet containing 10% kcal fat and 35% sucrose (product D12450Bi); or (3) high-fat low-sucrose (HFLS) diet containing 60% kcal fat and 7% sucrose (product D12492i).

Techniques: Marker

Journal: Disease Models & Mechanisms

Article Title: Independent effects of dietary fat and sucrose content on chondrocyte metabolism and osteoarthritis pathology in mice

doi: 10.1242/dmm.034827

Figure Lengend Snippet: Dietary sucrose and fat independently alter knee OA pathology. (A) Cartilage OA histopathology scoring of medial and lateral knee compartments. Osteophyte scoring from medial tibial compartment. Data points represent values for individual animals, and horizontal bars are mean±s.e.m. (B) Location-specific OA histopathology (LF, lateral femur; LT, lateral tibia; MF, medial femur; MT, medial tibia). Data are mean±s.e.m. (C-E) Representative sagittal section histology images from the lateral knee compartment. Scale bars: 100 µm. Dashed line rectangular area from the lateral tibial plateau is shown at higher magnification in the lower image to illustrate the greater prevalence of cartilage fibrillation (arrowheads) and Safranin-O staining loss (arrow) in the LFLS group than in the LFHS and HFLS groups. (F) Representative and maximal synovial lining cellularity and thickness. (G) Maximal focal synovial cellularity and thickness by joint compartment. Lines over bars indicate statistically significant differences (* P <0.05, ** P <0.01) by Kruskal–Wallis (A,F) or repeated-measures two-way ANOVA (B,G) with FDR-corrected post hoc tests (0.05). n =10 for each diet group, except for the LFLS group in F and G ( n =8).

Article Snippet: Beginning at 6 weeks of age, animals were fed one of three irradiated, purified open source diets (Research Diets Inc., USA; Table S1 ): (1) low-fat low-sucrose (LFLS) diet containing 10% kcal fat and 7% sucrose (product D12450Ji); (2) low-fat high-sucrose (LFHS) diet containing 10% kcal fat and 35% sucrose (product D12450Bi); or (3) high-fat low-sucrose (HFLS) diet containing 60% kcal fat and 7% sucrose (product D12492i).

Techniques: Histopathology, Staining

Journal: Disease Models & Mechanisms

Article Title: Independent effects of dietary fat and sucrose content on chondrocyte metabolism and osteoarthritis pathology in mice

doi: 10.1242/dmm.034827

Figure Lengend Snippet: Effects of dietary sucrose and fat on changes in metabolic and antioxidant enzyme abundance in knee cartilage. Heatmap of protein abundance levels as measured by selected-reaction-monitoring (SRM) mass spectrometry. Enzymes with a significant diet effect (one-way ANOVA; P <0.05) are shown, with relative abundance indicated by color scale. More diet-induced differences occurred with elevated dietary sucrose (20 proteins; LFHS versus LFLS) compared with dietary fat (7 proteins; HFLS versus LFLS). These differences were generally caused by protein levels being lower in the LFHS versus LFLS group, with HFLS group levels being intermediate. When comparing elevated dietary fat versus sucrose (i.e. HFLS versus LFHS), high dietary fat was associated with greater levels of proteins involved in glycolysis (Pfkl, Eno1), β-oxidation (Ech1, Hadha, Acaa2), and antioxidant defense (Gpx1). For β-oxidation enzymes, ‘p’ indicates localization to the peroxisome and ‘m’ indicates localization to mitochondria. Protein names and diet-specific differences based on Tukey post hoc statistical analysis are provided in Table S4 . TCA, tricarboxylic acid.

Article Snippet: Beginning at 6 weeks of age, animals were fed one of three irradiated, purified open source diets (Research Diets Inc., USA; Table S1 ): (1) low-fat low-sucrose (LFLS) diet containing 10% kcal fat and 7% sucrose (product D12450Ji); (2) low-fat high-sucrose (LFHS) diet containing 10% kcal fat and 35% sucrose (product D12450Bi); or (3) high-fat low-sucrose (HFLS) diet containing 60% kcal fat and 7% sucrose (product D12492i).

Techniques: Quantitative Proteomics, Targeted Proteomics, Mass Spectrometry

Journal: Disease Models & Mechanisms

Article Title: Independent effects of dietary fat and sucrose content on chondrocyte metabolism and osteoarthritis pathology in mice

doi: 10.1242/dmm.034827

Figure Lengend Snippet: Correlation-based network analysis of cartilage metabolic and stress-response antioxidant enzymes following high-sucrose and high-fat diets. Networks were developed based on significantly correlated protein pairs (i.e. correlation coefficient | r |≥0.8, P ≤0.05) among independent diet-specific cartilage samples analyzed by SRM mass spectrometry. (A) Graphical network representation for each diet. Squares represent one protein (i.e. ‘node’) with at least one significant correlation (i.e. ‘link’) to another protein. Enzyme functional categories and direction of correlation are indicated by the key. (B) Network density calculations show substantial diet effects, being greatest with a high-sucrose diet and least with a high-fat diet. (C) Venn diagram of the correlated enzyme pairs shows that most correlations are diet specific. (D) Network densities intrinsic to specific metabolic pathways. Carbohydrate metabolism and TCA cycle pathway densities were elevated for LFLS and LFHS diets, whereas fatty acid metabolism density was relatively greatest with a HFLS diet. (E) Diet-specific comparison of proteins with the greatest number of links to other proteins (i.e. ‘hub’ proteins). Full protein names are available in Table S4 .

Article Snippet: Beginning at 6 weeks of age, animals were fed one of three irradiated, purified open source diets (Research Diets Inc., USA; Table S1 ): (1) low-fat low-sucrose (LFLS) diet containing 10% kcal fat and 7% sucrose (product D12450Ji); (2) low-fat high-sucrose (LFHS) diet containing 10% kcal fat and 35% sucrose (product D12450Bi); or (3) high-fat low-sucrose (HFLS) diet containing 60% kcal fat and 7% sucrose (product D12492i).

Techniques: Mass Spectrometry, Functional Assay, Comparison