Metabolic and Hepatic Effects of Empagliflozin on Nonalcoholic Fatty Liver Mice

Figures & data

Figure 1 Empagliflozin ameliorated HFD-induced obesity and blood glucose. (A) Folding line graph of body weight change over time for each group of mice (n=9). The black arrow indicates the point in time when empagliflozin intervened. The ** on the first straight line indicates HFD vs NCD, P<0.01. **HFD vs NCD, p<0.01. ^&&HFD vs Empa, p<0.01. (B) Comparison of insulin levels in three groups of mice (n=8). (C) Comparison of fasting blood glucose levels in the three groups of mice (n=8). (D) IPTGG results. **HFD vs NCD, p<0.01. andand, HFD vs Empa, p<0.01. ns, P>0.05.

Abbreviation: IPTGG, Intraperitoneal glucose tolerance test.

Figure 2 Empagliflozin alleviated lipid profile, liver damage, inflammation and oxidative stress. (A) TC. (B) TG. (C) LDL-C. (D) HDL-C. (E) ALT. (F) AST. (G) Liver weight of mice. N=8/group. (H) MDA. (I) SOD. (J) TNF-α. (K) IL-6. (L) IL-1β. N=4/group. ns, P>0.05. **P<0.01.

Abbreviations: TC, total cholesterol; TG, triglyceride; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; ALT, alanine transaminase; AST, aspartate transaminase; SOD, superoxide dismutase; MDA, malondialdehyde; TNF-α, tumor necrosis factor-α; IL-6, interleukin-6; IL-1β, interleukin-1β.

Figure 3 Effects of empagliflozin on liver histology injuries. (A) HE staining. (B) Masson staining. (C) Oil red staining. (D) TEM images showed the mitochondria, mitochondrial microautophagy structure and ribosomes.

Abbreviation: TEM, Transmission electron microscopy.

Figure 4 Effects of empagliflozin on liver metabonomics. (A) PCA score plot. (B) OPLS-DA score plot (HFD/NCD group). (C) OPLS-DA score plot (Empa/HFD group). (D) Volcano plot (HFD/NCD group). (E) Volcano plot (Empa/HFD group). (F) Top 20 KEGG enrichment pathway bubble maps.

Abbreviations: PCA, Principal component analysis; OPLS-DA, Orthogonal partial least squares discriminant analysis; KEGG, Kyoto Encyclopedia of Genes and Genomes.

Table 1 Overlapping Differential Metabolites in the HFD/NCD and Empa/HFD Groups

KEGG	Metabolites	Average (H)	Average (C)	Average (E)	VIP	P value	Retention Time (min)
C00221	Beta-D-Glucose	436,245.73	182,323.58	289,723.53	1.06	<0.001	0.84
C00984	D-Galactose	928,185.01	292,536.14	593,863.28	1.70	0.0038	0.75
C00819	D-Glutamine	1,487,519.27	107,416.14	173,905.36	2.86	0.008	0.77
C05791	D-Urobilinogen	315,941	32,298.37	50,602.77	1.17	0.002	4.82
C00051	Glutathione	16,980,724.2	3,085,533.34	7,624,185.13	8.10	0.0005	0.88
C00670	Glycerophosphocholine	2,929,875.85	819,551.63	854,131.54	3.77	<0.001	0.77
C00064	L-Glutamine	190,897.36	21,085.46	28,705.84	1.01	0.01	0.75
C04230	LysoPC(16:0)	84,352,861.48	48,184,770.88	58,771,537.25	12.34	0.02	9.23
C04230	LysoPC(20:4(8Z,11Z,14Z,17Z)	88,329,477.42	47,148,201.84	52,247,988.03	13.7	0.009	8.74
C04230	PC(15:0/0:0)	4,523,500.23	2,547,397.06	3,162,383.62	2.89	0.02	9.237
C05790	Mesobilirubinogen	332,318.82	114,965.82	75,942.85	1.20	0.001	4.78
C00249	Palmitic acid	983,117.81	834,233.54	833,066.91	1.05	0.017	13.76
C01613	Stachyose	990,136.03	14,989.13	373,149.66	2.14	<0.001	0.76
C00422	TG(16:0/16:1(9Z)/18:1(9Z)	2,217,434.66	132,316.56	1,181,181.53	2.49	0.003	13.89
C02645	4,5-LTA4	474,530.93	97,192.03	43,513.80	1.59	0.008	10.08
C07220	Mexiletine	797,898.23	640,144.06	659,078.57	1.02	0.003	15.21
C06551	N-Ethyl trans-2-cis-6-nonadienamide	1,940,146.07	1,578,505.52	1,658,856.43	1.49	0.008	15.17
C10350	Monocrotaline	252,068.84	51,018.43	35,436.92	1.13	0.01	1.25
C00407	L-Isoleucine	1,334,228.07	15,857,001.71	16,613,429.22	4.45	0.002	1.49