Multi-omics investigation of spontaneous T2DM macaque emphasizes gut microbiota could up-regulate the absorption of excess palmitic acid in the T2DM progression
- Key Laboratory of Bio-resources and Eco-environment (Ministry of Education), College of Life Sciences, Sichuan University, China
- Sichuan Key Laboratory of Development and Application of Monkey Models for Human Major Disease, China
- SCU-SGHB Joint Laboratory on Non-human Primates Research, China
- Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, China
Figures
Figure 1 with 1 supplement
The changes in gut microbiota in spontaneous type 2 diabetes mellitus (T2DM) macaques.
(A) Alpha diversity estimates (Shannon index) between T2DM and control groups (ns, not significant, two-tailed t-test, n=8). (B) Alpha diversity estimates (Simpson index) between T2DM and control groups (ns, not significant, two-tailed t-test, n=8). (C) Principal Coordinate Analysis (PCoA) (n=8). (D) Differential analysis of gut microbial composition in T2DM and control groups (n=8). (E) LEfSe analysis between T2DM and control groups (n=8). (F) Differential analysis of gut microbial function in T2DM and control groups (n=5). The pathways with red color were associated with T2DM and inflammation. Error bar is mean with ± standard deviation (s.d.). (G) Differential analysis of gut microbial Carbohydrate-Active enZYme (CAZy) enzyme in T2DM and control groups (n=5). CBMs: carbohydrate-binding module (p=0.022, two-tailed t-test); GTs: Glycosyl Transferases (p=0.013, two-tailed t-test); PLs: Polysaccharide Lyases (p=0.017, two-tailed t-test); AA: Auxiliary activity enzymes (ns, not significant, two-tailed t-test); GH: Glycoside hydrolases (ns, not significant, two-tailed t-test); CE: Carbohydrate esterases (p=0.039, two-tailed t-test). For all boxplots: centre lines, upper and lower bounds show median values, 25th and 75th quantiles; upper and lower whiskers show the largest and smallest non-outlier values. In c, ellipses represent the 95% confidence intervals.
Figure 1—figure supplement 1
Metagenome analysis of microbiota.
(A) Differential microbes screened by metagenome analysis (p<0.05, two-tailed t-test). T2DM: type 2 diabetes mellitus. (B) The proportion of all metabolites. (C) Correlation analysis between differential untargeted metabolites and differential microbes (Spearman’s Rho). (D) Correlation analysis between differential targeted metabolites and differential microbes (Spearman’s Rho), *p<0.05. Data shown are from five individuals per group.
Figure 2 with 1 supplement
The alterations of fecal metabolites and gene expression in spontaneous type 2 diabetes mellitus (T2DM) macaques.
(A) Orthogonal partial least squares discriminant analysis (OPLS-DA) score plots based on the metabolic profiles. (B) Volcano plots of metabolomics (p<0.05, two-tailed t-test). (C) Fecal metabolites with significant differences between T2DM and control groups (VIP >1, p<0.05, two-tailed t-test). (D) Enrichment analysis of the differentially abundant pathways between T2DM and control groups (p<0.05, two-tailed t-test). (E) Non-metric multidimensional scaling (NMDS) analysis between T2DM and control groups (p=0.019, two-tailed t-test). (F) Volcano plots of DEGs (log fold change ≥1, p<0.05, two-tailed t-test). (G) The GO and KEGG pathway enrichment analyses (p<0.05, two-tailed t-test). (H) Weighted Gene Co-Expression Network Analysis (WGCNA). (I) Venn analysis between hub genes and DEGs. In A and E, ellipses represent the 95% confidence intervals. Data shown are from eight individuals per group.
Figure 2—figure supplement 1
Pathway enrichment analysis by aggregate fold change (AFC) and Weighted Gene Co-Expression Network Analysis (WGCNA).
(A) Total of 26 differential pathways were enriched (FDR<0.05). (B) The changes of gene expression in insulin resistance pathway compared to the control group, red color illustrating the up-regulation of genes and blue showed the down-regulation of genes in type 2 diabetes mellitus (T2DM) group, and the darker the color of the genes, the greater the |log10FC| value. (C) WGCNA functional enrichment. Data shown are from eight individuals per group.
Figure 3
Long-chain fatty acids (LCFAs) accumulation and inflammation occurred in spontaneous type 2 diabetes mellitus (T2DM) macaques.
(A–E) The contents of saturated fatty acid (SFA) (A, p=0.038), MUFA (B), PUFA (C), N3 (D), and N6 (E) in plasma (ns, not significant, two-tailed t-test). (F) The univariate analysis by two-tailed t-test, error bar is mean with ±s.d. (G) The multidimensional analysis by VIP value (VIP >1). (H–J) The contents of serum inflammatory cytokines, including IL-1β (H, p=0.032), TNF-α (I), and IL-6 (J) (ns, not significant, two-tailed t-test). (K) Correlation analysis between DEGs, differential metabolites, and differential microbes using Spearman rank correlation (|r|>0.5, adj p<0.05). For all boxplots: centre lines, upper and lower bounds show median values, 25th and 75th quantiles; upper and lower whiskers show the largest and smallest non-outlier values. Data shown are from seven to eight individuals per group.
Figure 4
The fecal microbiota transplanting (FMT) and high palmitic acid (PA) diet mice developed pre-type 2 diabetes mellitus (T2DM) characteristics.
(A) Experimental scheme of FMT and high PA diet treatment. (B–H) Metabolic analysis, including the trend of fasting plasma glucose (FPG) within 120 days (B), FPG (C, p=0.0003), oral glucose tolerance test (OGTT) (D), AUC of OGTT (E, p=0.028), fasting plasma insulin FPI (F, p=0.007), ITT (G), and body weight change (H) on day 120. (I–J) The contents of TC (I, p=0.005) and TG (J, p=0.041) in serum on day 120. (K, L) Representative H-E staining images of liver (K) and pancreas (L). For all boxplots: centre lines, upper and lower bounds show median values, 25th and 75th quantiles; upper and lower whiskers show the largest and smallest non-outlier values. Significance was determined using one-way ANOVA. In d, g, and h: *p<0.05, **p<0.01. Data shown are from four to six individuals per group.
Figure 5 with 2 supplements
The palmitic acid (PA) accumulation required the specific gut microbiota.
(A–C) Total PA contents in serum (A, p=0.013), ileum (B, p=0.016), and feces (C, p=0.014) on day 120. (D) Quantitative RT-PCR for Cd36 transcripts in ileum on day 120 (p=0.049). (E) The content of IL-17A in ileum on day 120 (p=0.027). For all boxplots: centre lines, upper and lower bounds show median values, 25th and 75th quantiles; upper and lower whiskers show the largest and smallest non-outlier values. Significance was determined using one-way ANOVA. Data shown are from three to four individual macaques per group. (F) Non-metric multidimensional scaling (NMDS) analysis (p=0.001, one-way ANOVA), ellipses represent the 95% confidence intervals. (G, H) LEfSe analysis between FTPA and control groups (G), FT and control groups (H). Data shown are from four individuals per group. (I) Specific gut microbiota structure promoted the absorption of excess PA by regulating the expression of IL-17A and Cd36, leading to the LCFAs accumulation and insulin resistance.
Figure 5—figure supplement 1
The changes in gut microbiota in FTPA, FT, and palmitic acid (PA)-treated mice.
(A) Alpha diversity estimates (Shannon index) (p>0.05, one-way ANOVA, n=4). (B) Alpha diversity estimates (Simpson index) between T2DM and control groups (p>0.05, one-way ANOVA, n=4). (C) Family level taxonomy and relative abundance of five groups. (D) The changes in members of the Lachnospiraceae family from day –14 to day 120. (E) LEfSe analysis between PA and control groups. For all boxplots: centre lines, upper and lower bounds show median values, 25th and 75th quantiles; upper and lower whiskers show the largest and smallest non-outlier values. Significance was determined using one-way ANOVA. Data shown are from four individuals per group.
Figure 5—figure supplement 2
The changes in gut microbiota in HFT-treated mice.
(A) Experimental scheme of fecal fecal microbiota transplanting (FMT) from control macaques. (B, C) The physiological characteristic of mice with different treatments, including body weight change (B), and trend of fasting plasma glucose (FPG) within 30 days (C). *p<0.05. (D–F) Changes in gut microbiota α-diversity and structure in mice, including Shannon index (p=0.0012) (D), Simpson index (p=0.0012) (E), and NMDS analysis (p=0.001, one-way ANOVA) (F). (G–I) Composition of gut microbiota in mice at phylum level (G), family level (H), and genus level (I). (J, K) The relative abundance of members in Lachnospiraceae between HTP and TP groups (J), control, HFT, FT, and FTPA groups on day 30 (K). (L, M) LEfSe analysis between pre-antibiotic (–14D) and post-antibiotic (0D) groups (L), HFT and FT groups on day 30 (M). For all boxplots: centre lines, upper and lower bounds show median values, 25th and 75th quantiles; upper and lower whiskers show the largest and smallest non-outlier values. Significance was determined using one-way ANOVA. Data shown are from three to nine individuals per group.
Figure 6
Integration of multi-omics results.
(A) Insulin resistance, fatty acid oxidation disorders, long-chain fatty acid s (LCFAs) accumulation, and inflammation occurred in spontaneous type 2 diabetes mellitus (T2DM) macaques. (B) Incomplete mitochondrial LCFAs β oxidation. The expression levels of fatty acid metabolism-related genes HADHB and ACSM3 were downregulated in spontaneous T2DM macaques, which could lead to accumulation of acylcarnitine, including l-propionylcarnitine, hexanoyl-l-carnitine, (r)-butyrylcarnitine, and isovaleryl-l-carnitine. (C) Gut inflammation. The decrease of Lactobacillus sp. likely caused the reduction of serotonin and indole-3-acetaldehyde, which promotes the expansion of palmitic acid (PA) producer Erysipelotrichacea and ultimately led to PA accumulation. Both Erysipelotrichacea and Ruminococcus gnavus (current name: Mediterraneibacter gnavus) promote the development of inflammation. Accumulation of PA and inflammation are important factors in the development of T2DM. (D) Accumulation of PA promoted the development of insulin resistance. In the PA-mTORC1-Akt pathway, the changes of RAP1A, SESTRIN3, and IRS1 expression promoted the development of insulin resistance in spontaneous T2DM macaques. The increase in PA promoted the development of T2DM by up-regulating the NF-κB signaling pathway.
Tables
Table 1
Physiological and biochemical parameters of Control and type 2 diabetes mellitus (T2DM) groups.
| Index | T2DM (n=8) | Control (n=8) |
|---|---|---|
| FPG (mmol/L) | 7.75±1 | 4.05±1.02** |
| FPI (μU/mL) | 17.97±8.50 | 6.45±2.56** |
| HOMA-IR | 6.24±3.06 | 1.20±0.65** |
| BMI | 14.03±7.71 | 14.30±1.42 |
| HbA1c (%) | 3.78±0.70 | 3.26±0.62 |
| TG (mmol/L) | 0.97±0.53 | 0.68±0.42 |
| TC (mmol/L) | 3.30±0.98 | 3.52±0.86 |
| HDL (mmol/L) | 1.23±0.40 | 1.42±0.38 |
| LDL (mmol/L) | 1.36±0.44 | 1.47±0.57 |
-
*p<0.05, **p<0.01.
-
FPG: fasting plasma glucose (normal range:≤6.1 mmol/L); FPI: fasting plasma insulin (normal range:≤12 μU/mL); HOMA-IR: homeostasis model assessment- insulin resistance (normal range: ≤2.67); BMI: body mass index; HbA1c: glycosylated hemoglobin A1c (normal range:<6.5%); TG: triglycerides (normal range: 0.95±0.47 mmol/L); TC: total cholesterol (normal range: 3.06±0.98 mmol/L); HDL: high-density lipoprotein cholesterol (normal range: 1.62±0.46 mmol/L); LDL: low-density lipoprotein cholesterol (normal range: 2.47±0.98 mmol/L). (Matsuda and DeFronzo, 1999; Lorenzo et al., 2012; Cowie et al., 2010; Yu et al., 2019).
Table 2
Blood routine examination of Control and type 2 diabetes mellitus (T2DM) groups.
| Index | T2DM (n=7) | Control (n=7) |
|---|---|---|
| WBC (10e9/L) | 15.63±4.66 | 11.32±2.19* |
| RBC (10e12/L) | 5.47±0.51 | 5.77±0.43 |
| HGB (g/L) | 129.57±15.48 | 136.71±9.60 |
| HCT (%) | 41.31±3.64 | 44.22±3.12 |
| MCV (fl) | 74.13±2.49 | 76.74±2.00 |
| MCH (pg) | 23.17±1.00 | 23.71±0.60 |
| MCHC (g/L) | 312.86±10.16 | 309±8.14 |
| RDW (%) | 15.23±2.12 | 14.69±1.74 |
| PLT (10e9/L) | 402±86.66 | 371.57±86.42 |
| MPV (fl) | 10.54±1.62 | 10.24±1.12 |
| PCT (%) | 0.42±0.08 | 0.38±0.09 |
| PDW (%) | 14.94±0.58 | 14.83±1.64 |
| LYM% (%) | 23.67±10.26 | 47.71±8.13** |
| LYM# (10e9/L) | 3.46±1.66 | 5.39±1.52* |
| MON% (%) | 4.18±3.34 | 6.18±2.29 |
| MON# (10e9/L) | 0.65±0.62 | 0.71±0.38 |
| NEU% (%) | 71.13±13.23 | 44.28±8.96** |
| NEU# (10e9/L) | 11.36±4.91 | 5.00±1.38** |
| EOS% (%) | 0.91±0.69 | 1.50±1.94 |
| EOS# (10e9/L) | 0.14±0.12 | 0.17±0.22 |
| BAS% (%) | 0.12±0.13 | 0.33±0.47 |
| BAS# (10e9/L) | 0.02±0.02 | 0.04±0.07 |
| NRBC# (10e9/L) | 0 | 0 |
| NRBC% (%) | 0 | 0 |
-
*p<0.05, **p<0.01.
-
WBC: white blood cell; RBC: red blood cell; HGB: hemoglobin; HCT: hematocrit; MCV: mean corpuscular volume; MCH: mean corpuscular hemoglobin; MCHC: mean corpuscular hemoglobin concentration; RDW: red blood cell distribution width; PLT: platelet; MPV: mean platelet volume; PCT: procalcitonin; PDW: platelet volume distribution width; LYM%: lymphocyte percentage; LYM#: lymphocyte value; MON%: monocytes percentage; MON#: monocytes value; NEU%: neutrophil percentage; NEU#: neutrophil value; EOS%: eoseosinophil percentage; EOS#: eoseosinophil value; BAS%: basophil percentage; BAS#: basophil value; NRBC%: nucleated red blood cell percentage; NRBC#: nucleated red blood cell value.
Table 3
Primers of RT-PCR.
| Gene name | Sequences of primers |
|---|---|
| CD36/F | 5’-ATGGGCTGTGATCGGAACTG-3’ |
| CD36/R | 5’-GTCTTCCCAATAAGCATGTCTCC-3’ |
| GADPH/F | 5’-CCTCGTCCCGTAGACAAAATG-3’ |
| GADPH/R | 5’-TCTCCACTTTGCCACTGCAA-3’ |
Table 4
RT-PCR reaction components.
| Reagent | Volume |
|---|---|
| 2× SG Fast qPCR Master Mix | 10.0 μL |
| DNF Buffer | 2.0 μL |
| F primer (10 μmol/L) | 0.4 μL |
| R primer (10 μmol/L) | 0.4 μL |
| cDNA | 1.0 μL |
| ddH2O | 6.2 μL |
Table 5
RT-PCR cycle procotol.
| Step | Temperature | Time |
|---|---|---|
| 1 | 95℃ | 3 min |
| 2 | 95℃ | 1–3 s |
| 3 | 60℃ | 30 s |
| 4 | ||
| 5 | 72℃ | 1 min |
Author response table 1
Differential analysis of palmitic acid and other fatty acids from fecal untargeted metabolomics in macaques.
| SuperClass | Class | SubClass | Names | log2FoldChange | p-value | VIP | Type | Significant |
|---|---|---|---|---|---|---|---|---|
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Palmitic acid | –0.449600 | 0.173730 | 0.881851 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | 2-hydroxypalmitic acid | –0.239318 | 0.408640 | 0.526705 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | 2-isopropylmalic acid | –0.651460 | 0.210910 | 1.348017 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Adipic acid | –0.621198 | 0.265750 | 1.385746 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Caproic acid | –1.115620 | 0.127570 | 1.625076 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | 12(13)-epoxy-9z-octadecenoic acid | –1.091521 | 0.905650 | 0.418656 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | 12s-hydroxy-5z,8e,10e-heptadecatrienoic acid | –1.489847 | 0.227590 | 1.278136 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | 18-carboxydinorleukotriene b4 | –0.401997 | 0.214310 | 1.193911 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | 5,8,11,14-eicosatetraynoic acid | –0.422578 | 0.250660 | 1.064897 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | 9-oxo-11-(3-pentyl-2-oxiranyl)–10e-undecenoic acid | –0.094902 | 0.670110 | 0.434639 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Behenic acid | –0.842212 | 0.649980 | 0.367039 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Cis-9-palmitoleic acid | –0.186967 | 0.560480 | 0.571173 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Dodeca-2(e),4(e)-dienoic acid | –0.131473 | 0.901130 | 0.033862 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Fumagillin | –0.105898 | 0.353840 | 0.952419 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Hymeglusin | –0.625361 | 0.030932 | 2.087180 | Down | yes |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Lignoceric acid | –1.247611 | 0.062477 | 1.858818 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Maresin 1 | –0.339035 | 0.950420 | 0.129840 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Monensin | –1.646496 | 0.021254 | 2.263949 | Down | yes |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Myriocin | –0.915527 | 0.023194 | 2.149777 | Down | yes |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Palmitic acid alkyne | –0.137112 | 0.937670 | 0.084572 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Tetradecanedioic acid | –0.403117 | 0.523220 | 0.602053 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Trans-traumatic acid | –0.208456 | 0.855200 | 0.314711 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Traumatic Acid | –0.382543 | 0.436360 | 0.696223 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | 10-hydroxy-4z,7z,11e,13z,16z,19z-docosahexaenoic acid | –0.295357 | 0.290920 | 0.589113 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | 11(12)-epoxy-5z,8z,14z,17z- eicosatetraenoic acid | –0.421126 | 0.459440 | 0.431261 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | 12,13-dihydroxy-9z-octadecenoic acid | –1.091521 | 0.905650 | 0.418656 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | 13-hydroxy-4z,7z,10z,14e,16z,19z-docosahexaenoic acid | –0.061835 | 0.825750 | 0.098187 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | 2-hydroxy-3-methylbutyric acid | –0.637274 | 0.522920 | 0.475814 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | 9-deoxy-9-methylene-16,16-dimethylprostaglandin e2 | –0.107350 | 0.932850 | 0.126214 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | .alpha.-keto-.gamma.-(methylthio)butyric acid | –0.797116 | 0.044712 | 1.973034 | Down | yes |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Azelaic acid | –0.250671 | 0.561220 | 0.516314 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Butanoic acid | –0.389470 | 0.408450 | 0.663941 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Cis,cis-muconic acid | –0.165996 | 0.907660 | 0.662026 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Dodecanedioic acid | –0.005762 | 0.783380 | 0.259046 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Dodecanoic acid | –0.674704 | 0.353100 | 0.982481 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Erucic acid | –0.236100 | 0.322980 | 0.672230 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Fa 18:1+3o | –0.080505 | 0.818690 | 0.244925 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Fahfa 34:0 | –0.284621 | 0.254680 | 0.680759 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Fahfa 36:1 | –0.165777 | 0.287690 | 0.657585 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Heptadecanoic acid | –0.686373 | 0.147130 | 0.880272 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Hexadecanedioic acid, 3,3,14,14-tetramethyl- | –0.166211 | 0.586710 | 0.156649 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Hydroxyisocaproic acid | –1.255793 | 0.322530 | 1.018523 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Isovaleric acid | –0.466135 | 0.217710 | 1.330000 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Mevalonic acid | –0.025494 | 0.669590 | 0.665701 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Myristic acid | –0.732180 | 0.156680 | 1.349036 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Octadecanedioic acid | –1.376197 | 0.105400 | 1.407770 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Octadecanoic acid | –0.172547 | 0.927540 | 0.308819 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Pentadecanoic acid | –0.367656 | 0.329110 | 0.535937 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Pimelic acid | –1.036139 | 0.041123 | 1.997825 | Down | yes |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Ricinoleic acid | –0.354777 | 0.678380 | 0.587595 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Sebacic acid | –0.278685 | 0.460530 | 0.460984 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | Tridecanoic acid (Tridecylic acid) | –1.592480 | 0.008072 | 2.035876 | Down | yes |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | (z)–5,8,11-trihydroxyoctadec-9-enoic acid | –0.026995 | 0.782280 | 0.161350 | Down | no |
| Lipids and lipid-like molecules | Fatty Acyls | Fatty acids and conjugates | 5-heptenoic acid, 7-[(1 r,2r,3s,5s)–2-[(1e,3s)–3-(2,3-dihydro-1h-inden-2-yl)–3-hydroxy-1-propen-1-yl]–3-fluoro-5-hydroxycyclopentyl]-, (5z)- | –0.150346 | 0.879000 | 0.246002 | Down | no |
Additional files
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Supplementary file 1
Information on the macaque samples.
- https://cdn.elifesciences.org/articles/104355/elife-104355-supp1-v1.xlsx
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Supplementary file 2
List of 64 differential metabolites.
- https://cdn.elifesciences.org/articles/104355/elife-104355-supp2-v1.xlsx
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Supplementary file 3
List of genes in four modules significantly correlated with T2DM.
- https://cdn.elifesciences.org/articles/104355/elife-104355-supp3-v1.xlsx
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Supplementary file 4
List of all identified untargeted metabolites.
- https://cdn.elifesciences.org/articles/104355/elife-104355-supp4-v1.xlsx
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Supplementary file 5
List of all targeted medium- and long-chain fatty acid metabolites.
- https://cdn.elifesciences.org/articles/104355/elife-104355-supp5-v1.xlsx
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MDAR checklist
- https://cdn.elifesciences.org/articles/104355/elife-104355-mdarchecklist1-v1.pdf
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Multi-omics investigation of spontaneous T2DM macaque emphasizes gut microbiota could up-regulate the absorption of excess palmitic acid in the T2DM progression
eLife 14:RP104355.
https://doi.org/10.7554/eLife.104355.4
