Sodium alginate prevents progression of non-alcoholic steatohepatitis and liver carcinogenesis in obese and diabetic mice

Abstract

Obesity and related metabolic abnormalities play a key role in liver carcinogenesis. Non-alcoholic steatohepatitis (NASH), which is often complicated with obesity and diabetes mellitus, is associated with the development of hepatocellular carcinoma (HCC). Sodium alginate (SA), which is extracted from brown seaweeds, is marketed as a weight loss supplement because of its high viscosity and gelling properties. In the present study, we examined the effects of SA on the progression of NASH and related liver carcinogenesis in monosodium glutamate (MSG)-treated mice, which show obesity, diabetes mellitus, and NASH-like histopathological changes. Male MSG-mice were intraperitoneally injected with diethylnitrosamine at 2 weeks of age, and, thereafter, they received a basal diet containing high- or low-molecular-weight SA throughout the experiment (16 weeks). At sacrifice, control MSG-treated mice fed the basal-diet showed significant obesity, hyperinsulinemia, steatosis and hepatic tumor development. SA administration suppressed body weight gain; improved insulin sensitivity, hyperinsulinemia, and hyperleptinemia; attenuated inflammation in the liver and white adipose tissue; and inhibited hepatic lipogenesis and progression of NASH. SA also reduced oxidative stress and increased anti-oxidant enzyme levels in the liver. Development of hepatic tumors, including liver cell adenoma and HCC, and hepatic pre-neoplastic lesions was significantly inhibited by SA supplementation. In conclusion, oral SA supplementation improves liver steatosis, insulin resistance, chronic inflammation, and oxidative stress, preventing the development of liver tumorigenesis in obese and diabetic mice. SA may have ability to suppress steatosis-related liver carcinogenesis in obese and diabetic subjects.

Preventive effects of the sodium glucose cotransporter 2 inhibitor tofogliflozin on diethylnitrosamine-induced liver tumorigenesis in obese and diabetic mice

“…Total RNA was isolated from the livers of the experimental mice and cell lines as reported previously [ 30 , 51 ]. qRT-PCR analysis was performed using previously reported specific primers for CCL2 , F4/80 , IL-1β , IL-6 , TNF-α , and 18S genes [ 51 , 52 ]. Other primer sequences are shown in Supplementary Table 2 .…”

A Review of the Alleged Health Hazards of Monosodium Glutamate

“…It was shown that diethylnitrosamine (DEN)‐induced liver tumorigenesis, in MSG‐treated mice, reflected steatosis‐related liver carcinogenesis in human (Figure ; Miyazaki et al., ). In a model that aimed to investigate the involvement of obesity‐related factors in colorectal cancer, newborn mice were administered MSG, 2 mg/g, s.c., for 4 days and azoxymethane (AOM), 15 mg/kg, i.p, a potent carcinogen that induces precancerous lesions in the colon.…”

<p>Dual SGLT1/SGLT2 Inhibitor Phlorizin Ameliorates Non-Alcoholic Fatty Liver Disease and Hepatic Glucose Production in Type 2 Diabetic Mice</p>

“…27 Later on, it was demonstrated that adult MSG mice develop insulin resistance with severe hyperglycemia, thus characterizing an obese T2D experimental model. 21,[28][29][30][31][32][33][34] Interestingly, the glycemic impairment occurs concurrently with hyperinsulinemia in T2D MSG-mice, 21,29,31,34 a profile not observed in T2D humans, in whom loss of glycemic control appears when plasma insulin concentrations begin to decrease. This difference is a consequence of the high replication capacity of beta cells in young mice in response to increased insulin requirements.…”