Volume 1, Issue 1
Article Type: Short commentary

Thrombospondin 1, obesity and nonalcoholic fatty liver disease

Konstanza Angelova^*

Department of Hygiene and Nutrition, Medical Faculty, Medical University, Bulgaria.

*Corresponding author:  Konstanza Angelova
Department of Hygiene and Nutrition, Medical Faculty, Medical University, 1431 Sofia, Bulgaria.
Email ID: kchristoangelova@gmail.com

Received: Feb 08, 2025
Accepted: Mar 05, 2025
Published Online: Mar 12, 2025
Journal: Annals of Nutrition and Dietetics
Copyright: Angelova K. © All rights are reserved Publication Model: Open Access

Citation: Angelova K. Thrombospondin 1, obesity and nonalcoholic fatty liver disease. Ann Nutr Diet. 2025; 1(1): 1001.

Short Commentary

The thrombospondin 1 (THBS1 or TSP-1), a subunit of a homotrimeric protein, is a multifunctional adhesive glycoprotein, encoded in humans by THBS1 gene [1]. It is a member of the thrombospondin family of five extracellular matrix proteins. THBS1 is produced and secreted in extracellular space by endothelial cells, adipocytes, fibroblasts, macrophages, hepatic stellate cells. The function of THBS1 is related to platelet aggregation and angiogenesis [2]. Subsequent studies found a mediation of adipose-derived thrombospondin 1 in insulin resistance and adipose inflammation [3,4]. Expression of THBS1 gene increases in obesity and insulin resistance [5]. Serum THBS1 has been estimated as biological marker of obesity and metabolic syndrome predominantly in women, with levels of THBS1 associated to abdominal obesity [6].

Obesity is a risk factor for Nonalcoholic Fatty Liver Disease (NAFLD). The prevalence of NAFLD in children and adolescents exceeds 36% in the context of obesity [7]. In most children, NAFLD is associated with insulin resistance, central or generalized obesity, and dyslipidemia with hypertriglyceridemia and low HDL-cholesterol levels [8]. In adult population, the impact of NAFLD shows a rapidly growing contribution to liver morbidity and mortality [9]. NAFLD remains undermanaged and is also lacking effective therapy.

Studies discovered that serum THBS1 levels increase in individuals with NAFLD and are positively correlated with the grades of liver steatosis [10]. Moreover, significant reduction of serum levels of THBS1 have been found with improvement of hepatic steatosis through lifestyle interventions. In experiment, pharmacological administration of recombinant human THBS1 attenuates lipid accumulation in primary hepatocytes and inhibits cleavage and processing of Sterol Regulatory Element-Binding transcription Factor 1 (SREBF1), (that regulates genes related to lipid and cholesterol production), through the mediation of CD36 (cluster of differentiation 36, or platelet glycoprotein 4, fatty acid translocase), involved in fatty acid metabolism.

The diverse functions of thrombospondin proteins have been attributed to several recognition motifs and domains of the genomic structure of THBS gene. Proteomics assists in the synthesis of mimetic peptide of THBS1 – ABT-526, which inhibits steatosis in hepatocytes exposed to high glucose and insulin [10].

Other studies confirm that extracellular protein THBS1 may be applied as an indicator of NAFLD [11]. But the pleiotropic functions and interactions of thrombospondin 1, including its role in angiogenesis and cancer development [12], suggest that various implications of THBS 1 as a therapeutic potential agent and risk factor for NAFLD should be further validated.

References

1. “Entrez Gene: THBS1 thrombospondin 1”, National Center for Biotechnology Information, US National Library of Medicine. ‘Human PubMed Reference’. https://www.ncbi.nlm.nih.gov/ gene/7057
2. Lawler J. The functions of thrombospondin-1 and -2. Curr Opin Cell Biol. 2000; 12: 634-40.
3. Inoue M, Jiang Y, Barnes RH, Tokunaga M, Martinez-Santibanez G, Geletka L, et al. Thrombospondin 1 mediates high-fat dietinduced muscle fibrosis and insulin resistance in male mice. Endocrinology 2013; 154: 4548-59.
4. Kong P, Gonzalez-Quesada C, Li N, Cavalera M, Lee DW, Frangogiannis NG. Thrombospondin-1 regulates adiposity and metabolic dysfunction in diet-induced obesity enhancing adipose inflammation and stimulating adipocyte proliferation. Am J Physiol Endocrinol Metab. 2013; 305: E439-50.
5. Varma V, Yao-Borengasser A, Bodles AM, Rasouli N, Phanavanh B, Nolen GT, et al. Thrombospondin-1 is an adipokine associated with obesity, adipose inflammation, and insulin resistance. Diabetes. 2008; 57: 432-9.
6. Matsuo Y, Tanaka M, Yamakage H, Sasaki Y, Muranaka K, Hata H, et al. Transpondin 1 as a novel biological marker of obesity and metabolic syndrome. Metabolism. 2015; 64:1490-99.
7. Shaunak M, Byrne CD, Davis N, Afolabi P, Faust SN, Davies JH. Non-alcoholic fatty liver disease and childhood obesity. Arch Dis Child. 2021; 106: 3-8.
8. Vos MB, Abrams SH, Barlow SE, Caprio S, Daniels SR, Kohli R, et al. NASPGHAN Clinical Practice Guideline for the Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease in Children. J Pediatr Gastroenterol Nutr. 2017; 64: 319-334.
9. Paik JM, Golabi P, Younossi Y, Mishra A, Younossi ZM. Changes in the global burden of chronic liver diseases from 2012 to 2017: The growing impact of NAFLD. Hepatology. 2020; 72: 1605-1616.
10. Bai J, Xia M, Xue Y, Ma F, Cui A, Sun Y, et al. Thronbospondin 1 improves hepatic steatosis in diet-induced insulin-resistant mice and is associated with hepatic fat content in humans. eBioMedicine/ Part of THE LANCET Discovery Science. 2020; 57: 102849.
11. Huang J, Li P, Chi J, Hu J, Cai H, Wu N, et al. A medical decision support platform for identifying thrombospondin 1 in non-alcoholic fatty liver disease via immune-infiltration analysis. J Vis Exp. 2024; 30.
12. Daubon T, Léon C, Clarke K, Andrique L, Salabert L, Darbo E, et al. Deciphering the complex role of thrombospondin-1 in glioblastoma development. Nature Communications. 2019; 10: 1146.