Study summary · research use only
AICAR ameliorates high-fat diet-associated pathophysiology in mouse and ex vivo models, independent of adiponectin
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this mouse and human ex vivo study, researchers examined 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an AMP-activated protein kinase activator, for effects on high-fat diet (HFD)-induced changes and adiponectin dependence. Six-week-old wild-type and Adipoq -/- mice received a 10% fat or 60% fat diet for 12 weeks plus AICAR (500 μg/g) three times per week from weeks 4-12; human adipose tissue from individuals with BMI 35-50 kg/m2 was incubated with AICAR (1 mmol/l) for 6 h at 37°C. AICAR was associated with an M1-to-M2 macrophage switch, reduced CD8+ T cell infiltration, partially restored glucose tolerance, and reduced albuminuria, urinary H2O2, and renal superoxide (p<0.05, p<0.05, p<0.01) in both mouse genotypes, independent of adiponectin, and with an M1-to-M2 switch and reduced TNF-alpha in human tissue explants. Trial registration NCT02322073.
Abstract
In this study, we aimed to evaluate the therapeutic potential of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMP-activated protein kinase, for ameliorating high-fat diet (HFD)-induced pathophysiology in mice. We also aimed to determine whether the beneficial effects of AICAR were dependent on adiponectin. Furthermore, human adipose tissue was used to examine the effect of AICAR ex vivo. Six-week-old male C57BL/6J wild-type and Adipoq -/- mice were fed a standard-fat diet (10% fat) or an HFD (60% fat) for 12 weeks and given vehicle or AICAR (500 μg/g) three times/week from weeks 4-12. Diet-induced pathophysiology was examined in mice after 11 weeks by IPGTT and after 12 weeks by flow cytometry and western blotting. Human adipose tissue biopsies from obese (BMI 35-50 kg/m2) individuals were incubated with vehicle or AICAR (1 mmol/l) for 6 h at 37°C, after which inflammation was characterised by ELISA (TNF-α) and flow cytometry. AICAR attenuated adipose inflammation in mice fed an HFD, promoting an M1-to-M2 macrophage phenotype switch, while reducing infiltration of CD8+ T cells. AICAR treatment of mice fed an HFD partially restored glucose tolerance and attenuated hepatic steatosis and kidney disease, as evidenced by reduced albuminuria (p < 0.05), urinary H2O2 (p < 0.05) and renal superoxide levels (p < 0.01) in both wild-type and Adipoq -/- mice. AICAR-mediated protection occurred independently of adiponectin, as similar protection was observed in wild-type and Adipoq -/- mice. In addition, AICAR promoted an M1-to-M2 macrophage phenotype switch and reduced TNF-α production in tissue explants from obese human patients. AICAR may promote metabolic health and protect against obesity-induced systemic diseases in an adiponectin-independent manner. Furthermore, AICAR reduced inflammation in human adipose tissue explants, suggesting by proof-of-principle that the drug may reduce obesity-induced complications in humans. ClinicalTrials.gov NCT02322073.
pepmg summarizes the peer-reviewed literature and links to every source — it sells nothing, ships nothing, and gives no medical, dosing, or human-use guidance. Don't just trust this summary: follow the citation to its source and read it yourself. Research use only.