ArticleDiabetologia2018
Angptl8 antisense oligonucleotide improves adipose lipid metabolism and prevents diet-induced NAFLD and hepatic insulin resistance in rodents.
Article in Diabetologia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48 citing papers in PubMed, 81 citations in OpenAlex.
- Antisense Oligonucleotide Therapeutics Targeting Age-Related Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Angiopoietin-like 8 governs osteoblast-adipocyte lineage commitment during skeletal aging.JCI insight · 2025Article
- Impact of Tumor Necrosis Factor Antagonist Therapy on Circulating Angiopoietin-like Protein 8 (ANGPTL8) Levels in Crohn's Disease-A Prospective Multi-Center Study.Journal of clinical medicine · 2025Article
- Understanding the Role of Adipokines in Cardiometabolic Dysfunction: A Review of Current Knowledge.Biomolecules · 2025Review
- Angiopoietin-like protein 8 directs DNA damage responses towards apoptosis by stabilizing PARP1-DNA condensates.Cell death and differentiation · 2025Article
- Adipokine/hepatokines profiling of fatty liver in adolescents and young adults: cross-sectional and prospective analyses of the BCAMS study.Hepatology international · 2025Article
- Pathogenetic therapeutic approaches for endocrine diseases based on antisense oligonucleotides and RNA-interference.Frontiers in endocrinology · 2025Review
- Adipocyte Angptl8 deletion improves glucose and energy metabolism and obesity associated inflammation in mice.iScience · 2024Article
- Inhibition of the ANGPTL3/8 Complex for the Prevention and Treatment of Atherosclerotic Cardiovascular Disease.Current atherosclerosis reports · 2024Review
- Updates on Rare Genetic Variants, Genetic Testing, and Gene Therapy in Individuals With Obesity.Current obesity reports · 2024Review
- Metabolic Crosstalk between Liver and Brain: From Diseases to Mechanisms.International journal of molecular sciences · 2024Review
- Transcriptomic Analyses Reveal the Effects of Walnut Kernel Cake on Adipose Deposition in Pigs.Genes · 2024Article
- Review
- Predictive value of angiopoietin-like protein 8 in metabolic dysfunction-associated fatty liver disease and its progression: A case-control study.World journal of diabetes · 2024Article
- Hepatokines: the missing link in the development of insulin resistance and hyperandrogenism in PCOS?Hormones (Athens, Greece) · 2023Review
- ANGPTL8 accelerates liver fibrosis mediated by HFD-induced inflammatory activity via LILRB2/ERK signaling pathways.Journal of advanced research · 2023Article
- Adolescent obesity and ANGPTL8: correlations with high sensitivity C-reactive protein, leptin, and chemerin.Frontiers in endocrinology · 2023Article
- Emerging insights into the roles of ANGPTL8 beyond glucose and lipid metabolism.Frontiers in physiology · 2023Review
- ANGPTL8 is a negative regulator in pathological cardiac hypertrophy.Cell death & disease · 2022Article
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
aims/hypothesisTargeting regulators of adipose tissue lipoprotein lipase could enhance adipose lipid clearance, prevent ectopic lipid accumulation and consequently ameliorate insulin resistance and type 2 diabetes. Angiopoietin-like 8 (ANGPTL8) is an insulin-regulated lipoprotein lipase inhibitor strongly expressed in murine adipose tissue. However, Angptl8 knockout mice do not have improved insulin resistance. We hypothesised that pharmacological inhibition, using a second-generation antisense oligonucleotide (ASO) against Angptl8 in adult high-fat-fed rodents, would prevent ectopic lipid accumulation and insulin resistance by promoting adipose lipid uptake.
methodsANGPTL8 expression was assessed by quantitative PCR in omental adipose tissue of bariatric surgery patients. High-fat-fed Sprague Dawley rats and C57BL/6 mice were treated with ASO against Angptl8 and insulin sensitivity was assessed by hyperinsulinaemic-euglycaemic clamps in rats and glucose tolerance tests in mice. Factors mediating lipid-induced hepatic insulin resistance were assessed, including lipid content, protein kinase Cε (PKCε) activation and insulin-stimulated Akt phosphorylation. Rat adipose lipid uptake was assessed by mixed meal tolerance tests. Murine energy balance was assessed by indirect calorimetry.
resultsOmental fat ANGPTL8 mRNA expression is higher in obese individuals with fatty liver and insulin resistance compared with BMI-matched insulin-sensitive individuals. Angptl8 ASO prevented hepatic steatosis, PKCε activation and hepatic insulin resistance in high-fat-fed rats. Postprandial triacylglycerol uptake in white adipose tissue was increased in Angptl8 ASO-treated rats. Angptl8 ASO protected high-fat-fed mice from glucose intolerance. Although there was no change in net energy balance, Angptl8 ASO increased fat mass in high-fat-fed mice. CONCLUSIONS/
interpretationDisinhibition of adipose tissue lipoprotein lipase is a novel therapeutic modality to enhance adipose lipid uptake and treat non-alcoholic fatty liver disease and insulin resistance. In line with this, adipose ANGPTL8 is a candidate therapeutic target for these conditions.
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