Background & Aims: Thrombospondin 1 (TSP1) is a multifunctional matricellular protein. We previously showed that TSP1 has an important role in obesity-associated metabolic complications, including inflammation, insulin resistance, cardiovascular, and renal disease. However, its contribution to obesity-associated non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD or NASH) remains largely unknown; thus, we aimed to determine its role.
Methods: High-fat diet or AMLN (amylin liver NASH) diet-induced obese and insulin-resistant NAFLD/NASH mouse models were utilised, in addition to tissue-specific -knockout mice, to determine the contribution of different cellular sources of obesity-induced TSP1 to NAFLD/NASH development.
Results: Liver TSP1 levels were increased in experimental obese and insulin-resistant NAFLD/NASH mouse models as well as in obese patients with NASH. Moreover, TSP1 deletion in adipocytes did not protect mice from diet-induced NAFLD/NASH. However, myeloid/macrophage-specific TSP1 deletion protected mice against obesity-associated liver injury, accompanied by reduced liver inflammation and fibrosis. Importantly, this protection was independent of the levels of obesity and hepatic steatosis. Mechanistically, through an autocrine effect, macrophage-derived TSP1 suppressed expression in liver, which amplified liver proinflammatory signalling (Toll-like receptor 4 signal pathway) and promoted NAFLD progression.
Conclusions: Macrophage-derived TSP1 is a significant contributor to obesity-associated NAFLD/NASH development and progression and could serve as a therapeutic target for this disease.
Lay Summary: Obesity-associated non-alcoholic fatty liver disease is a most common chronic liver disease in the Western world and can progress to liver cirrhosis and cancer. No treatment is currently available for this disease. The present study reveals an important factor (macrophage-derived TSP1) that drives macrophage activation and non-alcoholic fatty liver disease development and progression and that could serve as a therapeutic target for non-alcoholic fatty liver disease/steatohepatitis.
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http://dx.doi.org/10.1016/j.jhepr.2020.100193 | DOI Listing |
Drug Des Devel Ther
January 2025
Clinical Research Center, Shijiazhuang Fifth Hospital, Shijiazhuang, Hebei, People's Republic of China.
Non-alcoholic fatty liver disease (NAFLD) is the major cause of chronic liver disease worldwide, with no universally recognized effective treatments currently available. In recent years, ginseng and its principal active components, such as ginsenosides, have shown potential protective effects in the treatment of these liver diseases. In NAFLD, studies have demonstrated that ginseng can improve hepatic lipid metabolism, reduce inflammatory responses, and inhibit oxidative stress and fibrosis, thereby attenuating the progression of NAFLD.
View Article and Find Full Text PDFFood Sci Nutr
January 2025
Laboratory of Biotechnology and Natural Resources Valorization, Faculty of Sciences Ibn Zohr University Agadir Morocco.
Hepatic steatosis/non-alcoholic fatty liver disease is a major public health delinquent caused by the excess deposition of lipid into lipid droplets (LDs) as well as metabolic dysregulation. Hepatic cells buildup with more fat molecules when a person takes high fat diet that is excessive than the body can handle. At present, millions of people in the world are affected by this problem.
View Article and Find Full Text PDFCureus
December 2024
Faculty of Health Education and Life Sciences, Post-Qualifying Healthcare Practice, Birmingham City University, Birmingham, GBR.
Background: There are no studies investigating missed opportunities for earlier diagnosis in newly/recently detected Type 2 Diabetes Mellitus and Non-alcoholic Fatty Liver Disease in the region of Bihar, India.
Methods: This study is a single-center cross-sectional study undertaken at the Research Centre for Diabetes Hypertension and Obesity, Samastipur, Bihar, India. The study collected data from newly/recently diagnosed persons with T2DM.
Euroasian J Hepatogastroenterol
December 2024
Department of Gastroenterology and Hepatology, Dr. Ziauddin Hospital Clifton Campus, Karachi, Pakistan.
Background: Fat accumulation in the liver is affecting 38% of the global population. It can also occur in normal-weight individuals, termed lean non-alcoholic fatty liver disease (NAFLD). This study examines Asian and Western body mass index (BMI) criteria, as well as metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) diagnostic guidelines, in lean fatty liver cases within a healthcare setting.
View Article and Find Full Text PDFToxicol Res
January 2025
Department of Biochemistry, College of Natural Sciences, Kangwon National University, 24341 Chuncheon, Republic of Korea.
Unlabelled: Lipopolysaccharide (LPS), a gut-derived endotoxin, is a recognized risk factor for both Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). Rocaglamide-A (Roc-A), a natural compound derived from the genus Aglaia, is known for its pharmacological and immunosuppressive effects on various cell types. Although our recent investigations have unveiled Roc-A's anti-adipogenic role in adipocytes, its mechanism in hepatic inflammation remains elusive.
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