A Nutraceutical Formulation Containing Brown Algae Reduces Hepatic Lipid Accumulation by Modulating Lipid Metabolism and Inflammation in Experimental Models of NAFLD and NASH

Abstract

Recently, some preclinical and clinical studies have demonstrated the ability of brown seaweeds in reducing the risk factors for metabolic syndrome. Here, we analyzed the beneficial effect of a nutraceutical formulation containing a phytocomplex extracted from seaweeds and chromium picolinate in animal models of liver steatosis of differing severities (rats with non-alcoholic fatty liver disease (NAFLD) and its complication, non-alcoholic steatohepatitis (NASH)). This treatment led to a significant drop in hepatic fat deposition in both models (p < 0.01 vs. untreated animals), accompanied by a reduction in plasma inflammatory cytokines, such as interleukin 6, tumor necrosis factor α, and C reactive protein, and myeloperoxidase expression in liver tissue. Furthermore, a modulation of the molecular pathways involved in lipid metabolism and storage was demonstrated, since we observed the significant reduction of the mRNA levels of fatty acid synthase, diacylglycerol acyltransferases, the sterol-binding protein SREBP-1, and the lipid transporter perilipin-2, in both treated NAFLD and NASH rats in comparison to untreated ones. In conclusion, this nutraceutical product was effective in reducing liver steatosis and showed further beneficial effects on hepatic inflammation and glycemic control, which were particularly evident in rats characterized by a more severe condition, thus representing a therapeutic option for the treatment of NAFLD and NASH patients.

Association between blood chromium and hepatic steatosis assessed by liver ultrasound transient elastography: National Health and Nutrition Examination Survey 2017–2020

“…Cr supplementation decreased the expression of liver nuclear factor kappa-B (NF-κB) p65, and lowered plasma levels of C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), and intercellular cell adhesion molecule-1 (ICAM-1) in animal models of obesity, metabolic syndrome and T2DM. Furthermore, Cr supplementation downregulates CD68 and myelo-peroxidase (MPO) protein expression, reduces levels of pro-inflammatory cytokines in serum, and increases the secretion of the anti-inflammatory cytokine in hepatic steatosis animal models ( 8 , 23 , 24 , 27 , 28 ).…”

“…Cr affects energy metabolism and suppresses hepatic lipid deposition by modulating glucolipid metabolism-related enzymes. Cr supplementation inhibits the activities of α-amylase and α-glucosidase, exerting a beneficial effect on postprandial blood glucose ( 28 , 29 ). In animal models of metabolic syndrome and T2DM, Cr supplementation inhibited hepatic gluconeogenesis by decreasing mRNA expression of fructose 1,6-bisphosphatase (FBPase), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pase) and promoted hepatic glycogen synthesis by upregulating glucokinase (Gk) mRNA expression in the liver ( 32 – 34 ).…”

“…In addition, Cr reduced the expression of CD36 in liver tissue and SMMC-7721 cells, thus decreasing the uptake of exogenous fatty acids, while increasing the levels of liver type fatty acid binding protein (L-FABP) mRNA in liver tissue, promoting fatty acid transport across cell membranes and into mitochondria, which enhanced hepatic fatty acid utilization ( 8 , 33 – 36 ). In animal models of NAFLD and metabolic syndrome, Cr supplementation downregulated the expression of sterol regulatory element-binding protein-1 (SREBP-1) mRNA, which is a key transcription factors involved in the synthesis of cholesterol and fatty acids ( 28 , 33 , 37 ). In animal models of NAFLD and non-alcoholic fatty liver hepatitis (NASH), Cr downregulated the mRNA expression of diacylglycerolacyltransferase (DGAT)-1, DGAT-2, and fatty acid synthase (FASN), while suppressed protein expression of perilipin-2 (PLIN-2), consequently lessening the storage of TG in liver tissue ( 28 ).…”

“…In animal models of NAFLD and metabolic syndrome, Cr supplementation downregulated the expression of sterol regulatory element-binding protein-1 (SREBP-1) mRNA, which is a key transcription factors involved in the synthesis of cholesterol and fatty acids ( 28 , 33 , 37 ). In animal models of NAFLD and non-alcoholic fatty liver hepatitis (NASH), Cr downregulated the mRNA expression of diacylglycerolacyltransferase (DGAT)-1, DGAT-2, and fatty acid synthase (FASN), while suppressed protein expression of perilipin-2 (PLIN-2), consequently lessening the storage of TG in liver tissue ( 28 ). Furthermore, Cr enhances cholesterol metabolism.…”

“…Noteworthily, smoking primarily induces ectopic deposition of lipids in the liver through the induction of inflammation, oxidative stress, gut microbiota dysbiosis, disturbances in glucose and lipid metabolism and insulin resistance ( 40 , 41 ). Additionally, the pulmonary Cr may alleviate the toxic effects of nicotine on liver by multiple ways ( 24 , 28 , 34 , 42 ). However, the specific mechanism by which nicotine affects the interactivities between blood Cr and liver steatosis is still unclear.…”