PMC

(A) Comparison of lean MAFLD and lean NAFLD with different high-risk factors in the baseline diagnosed patients. (B) Comparison of lean MAFLD and lean NAFLD with different high-risk factors in the follow-up newly diagnosed cases. *p<0.05 for lean MAFLD vs. lean NAFLD. T2DM, type 2 diabetes; WC, waist circumference.

Inflammatory and metabolic profile in adipose tissue of OB CIA mice. Inflammation, presence and polarization of macrophages, and glucose and lipid metabolisms. (A) mRNA relative expression of TNF-α in white adipose tissue of control lean, Lean CIA, OB, and OB CIA, (B) mRNA relative expression of IL-1β white adipose tissue of control lean, Lean CIA, OB, and OB CIA, (C) mRNA relative expression of F4/80 in white adipose tissue of control lean, Lean CIA, OB, and OB CIA, (D) ratio of CD11c/CD206 mRNA relative expression in white adipose tissue of control lean, Lean CIA, OB, and OB CIA, (E) ratio of CD11c/CD209e mRNA relative expression in white adipose tissue of control lean, Lean CIA, OB, and OB CIA, (F) mRNA relative expression of FAS in white adipose tissue of control lean, Lean CIA, OB, and OB CIA, (G) mRNA relative expression of PPARγ in white adipose tissue of control lean, Lean CIA, OB, and OB CIA, (H) mRNA relative expression of HSL in white adipose tissue of control lean, Lean CIA, OB, and OB CIA, (I) mRNA relative expression of ATGL in white adipose tissue of control lean, Lean CIA, OB, and OB CIA, (J) correlation between the mRNA expression of HSL and TNF-α in white adipose tissue of lean CIA, (K) correlation between the mRNA expression of HSL and TNF-α in white adipose tissue of OB CIA, (L) mRNA relative expression of IRS-1 in white adipose tissue of control lean, Lean CIA, OB, and OB CIA, (M) mRNA relative expression of IRS-2 in white adipose tissue of control lean, Lean CIA, OB, and OB CIA, and (N) mRNA relative expression of GLUT-4 in white adipose tissue of control lean, Lean CIA, OB, and OB CIA. CIA, collagen induced arthritis; OB, obese; TNF-α, tumor necrosis factor alpha; IL-1β, interleukin 1 beta; F4/80, cell surface glycoprotein F4/80; CD, cluster differentiation; FAS, fatty acid synthase; PPARγ, Peroxisome Proliferator Activated Receptor Gamma; HSL, hormone sensitive lipase; ATGL, adipose triglyceride lipase; IRS-1, insulin receptor substrate 1; GLUT-4, glucose transporter type 4. Significance was determined by one-way ANOVA followed by Ducan post hoc test (A–I, L–N). ^aSignificant differences vs. lean (p < 0.05). ^bSignificant differences vs. lean CIA (p < 0.05). ^cSignificant differences vs. OB (p < 0.05).

(A) Body weights of 6- to 24-week-old lean control and Mac-IKO male mice (n=9–16). (B) Body compositions (fat, lean, and fluid mass) of 24-week-old lean control and Mac-IKO male mice as measured by MRI (n=9–16). (C) Organ weights of 24-week-old lean control and Mac-IKO male mice (n=9–16). All data are presented as mean + SD. (D) Body weights of 12- to 26-week old lean control and Adipo-IKO male mice. n=5/genotype. (E) Body compositions of 26-week-old lean control and Adipo-IKO male mice. n=5/genotype. (F) Organ weights of 26-week-old lean control and Adipo-IKO mice. n=5/genotype. All data are presented as mean + SD.

a Box plot of the OxA levels in lean + vehicle (lean), lean + OxA (40 µg/kg, i.p), HFD + vehicle, ob/ob, ob/ob + Lep (5 mg/kg). lean + veh: 4.82 ± 0.1 pmol/mg, lean + OxA: 10.10 ± 0.8 pmol/mg, HFD + vehicle = 10.57 ± 0.2 pm/mg, ob/ob + veh: 11 + 0.2 pmol/mg, ob/ob + leptin 5.02 ± 0.1 pmol/mg. n = 21 (7 mice per group in triplicate), ANOVA test and Bonferroni post hoc test, ****p < 0.0001, F = 222.1. b Representative fEPSPs recorded before and after the induction of the LTP in lean, lean + OxA 100 nM, lean + OxA 200 nM, lean + OxA 200 nM + SB 10 μM. c Plot of the fEPSP slope recorded in brain slice before and after the induction of the LTP (time 0) in the DG of lean slices, lean + OxA (100 nM), lean + OxA (200 nM) and lean + OxA + SB (200 nM OxA + SB 10 µM). n = 10 slices from four mice (lean), n = 8 slices from four mice (lean + OxA 100 nM), n = 11 slices from five mice (lean+ 200 nM OxA or lean+ 200 nM OxA+ SB), data are presented as mean values ± SEM. d Box plot of the LTP in the four experimental conditions plotted in (c). n = 10 slices from four mice (lean), slope 40−60 min post HFT: 120.5% ± 6.938% from control slices, n = 8 slices from four mice (lean + OxA 100 nM), slope 40−60 min post HFT: 116.8% ±  6.938%, n = 11 slices from five mice for lean+ 200 nM OxA and lean+ 200 nM OxA +SB groups, slope 40−60 min post HFT: 91.83% ± 6.933% and 116.1% ± 7.023% respectively. *p < 0.05; ANOVA with Bonferroni post hoc test, F = 4.90. e−g Confocal images of DCX/OxA/CB1 immunolabeling of dentate gyrus (DG) showing a wide density of distribution of CB1/DCX-ir (light blue, arrow) or OxA/DCX-ir (yellow-orange, arrowhead) colocalizing puncta in the IML-MML of lean (e) and obese (f, g) mice. e₁−g₂ High-power fluorescent micrographs of orthogonal stacks are shown for each respective (e−g) area; dotted lines and crosshairs are used to show 3D coordinates and define the area of interest indicated by arrows 1 and arrowheads 2 which correspond to numbered insets in (e−g). Scale bar: 10 μm (e−g) and 2 μm (e₁−g₂). h−j Graphs showing the percentage of CB1/DCX-ir or OxA/DCX-ir or CB1/OxA/DCX-ir colocalizing area/µm² of DCX-ir area in the IML-MML (h), or OxA-ir area/µm² of IML-MML area (i), or CB1/VGluT1 colocalizing area/µm² of VGluT1-ir area in the IML-MML (j), in lean and obese mice. Graphs show box-whisker plots (including minima, maxima, and median values, lower and upper quartiles) with single values. Data are mean of the percentage ± percentage of SEM from n = 30 slices in six mice per group; Kruskal−Wallis test and post hoc Dunn’s test, ****p  < 0.0001). k, l Confocal images of VGluT1/NeuroD/CB1 immunolabeling of DG in lean (k) and obese ob/ob mice (l) showing a wide density of distribution of CB1/VGluT1 (light blue) colocalizing puncta in the IML-MML. Scale bar: 200 µm. Immunolabeling was repeated n = 3 times, independently in different DG sections from n = 6 mice per group, with similar results. The box plots elements are: center line, median (Q2); square symbol, mean; box limits, 25th (Q1)−75th (Q3) percentiles; whisker length is determined by the outermost data points. Source data are provided as a Source Data file.