Fig 2: Mat1a antisense oligonucleotides reverse obesity and hepatoesteatosis in ob/ob mice.Three-month-old B6.Cg-Lepob/J (ob/ob) mice were fed a high-fat diet (HFD) for 4 weeks. During the diet mice were treated with Mat1a antisense oligonucleotide (ASO) or control ASO (25 mg/kg/week) until sacrifice. a Body weight change and body weight for HFD-fed control (n = 5) and Mat1a (n = 5) ASO-treated ob/ob mice. b Food intake for HFD-fed control (n = 2 cages) and Mat1a (n = 2 cages) ASO-treated ob/ob mice. c Glucose (GTT) and d insulin tolerance tests (ITT) in HFD-fed control (n = 5) and Mat1a (n = 5) ASO-treated ob/ob mice. Data are also indicated as area under the curve (AUC) expressed in arbitrary units (A.U.). e Serum insulin levels in HFD-fed control (n = 5) and Mat1a (n = 5) ASO-treated ob/ob mice fasted overnight. f Representative microphotographs of liver sections stained for Sudan III and liver triglyceride (TG) concentration of HFD-fed control (n = 5) and Mat1a (n = 5) ASO-treated ob/ob mice. g BAT fatty acid ß-oxidation, determined measuring the amount of [14C]-acid-soluble metabolites (ASM) (incomplete oxidation of palmitate) and [14C]-CO2 (complete oxidation of palmitate) in HFD-fed control (n = 5) and Mat1a (n = 4) ASO-treated ob/ob mice. h Representative blots and densitometries of uncoupling protein1 (UCP1) and tubulin in BAT of HFD-fed control (n = 9) and Mat1a (n = 9) ASO-treated ob/ob mice. i mRNA expression levels in BAT of HFD-fed control (n = 9) and Mat1a (n = 9) ASO-treated ob/ob of mice Ucp1, PR/SET Domain 16 (Prdm16), peroxisome proliferator-activated receptor (PPAR) gamma co-activator 1 (Ppargc1a) and PPAR alpha (Ppara) as indicators of thermogenesis and fatty acid ß-oxidation; and PPAR gamma (Pparg) and adiponectin (Adipoq), as indicators of adipocyte differentiation. Results were normalized with Actin (Actb). Values are presented as means ± SEM for time course representations, and as means ± SD for histograms. Statistically significant differences between groups are indicated by *p < 0.05, **p < 0.01, and ***p < 0.001 (two-tailed Student’s test). Statistical analysis performed by two-way ANOVA test comparing Control ASO HFD vs. Mat1a ASO HFD is presented in GTT and ITT curves. Source data are provided as a Source data file.

Fig 3: Body and liver weight changes, and biochemical profile in Bitter Melon Juice (BMJ)-treated high fat diet-induced obese (DIO) C57BL/6J mice. A) Relative body weight changes in DIO vs. BMJ + DIO mice. B) Relative liver weights of DIO vs. BMJ + DIO mice (left panel); Representative pictographs (x100) of hematoxylin and eosin (H&E) stained hepatic tissue; magnified images depicted at x400 magnification highlight the appearance of fatty globules/steatosis (right panel). Arrows indicate bulging cells with large globules filled with lipid content; scale bar: 50 µM C) Relative serum levels of metabolic parameters and adipokines in DIO vs. BMJ + DIO mice. BMJ was given for 40 days as oral gavage: 200 mg/kg body wt). DIO, diet-induced obesity; Glc, glucose; TGA, triglycerides; AdipoQ, Adiponectin. **p < 0.02; *p < 0.05. n = 4 per group.

Fig 4: Effect of UAL on the expression of functional genes in 3T3-L1 cells. 3T3-L1 cells were differentiated for 4 days and treated with UAL for 24 h. Metformin was used as positive control. Relative expression of Pparg (A), Cebpa (B), Adipoq (C), Ppara (D), Srebf1 (E), Acaca (F), Fasn (G) Lep (H), Ppargc1a (I), Ucp1 (J) mRNA transcripts is shown. Values are expressed as mean ± SEM of three independent experiments. * p < 0.05, ** p < 0.01, *** p < 0.001 compared with DIFFERENTIATED (ANOVA with Dunnett´s post hoc test).