ABSTRACT
Obesity is a top public health concern, and a molecule that safely treats obesity is urgently needed. Disulfiram (known commercially as Antabuse), an FDA-approved treatment for chronic alcohol addiction, exhibits anti-inflammatory properties and helps protect against certain types of cancer. Here, we show that in mice disulfiram treatment prevented body weight gain and abrogated the adverse impact of an obesogenic diet on insulin responsiveness while mitigating liver steatosis and pancreatic islet hypertrophy. Additionally, disulfiram treatment reversed established diet-induced obesity and metabolic dysfunctions in middle-aged mice. Reductions in feeding efficiency and increases in energy expenditure were associated with body weight regulation in response to long-term disulfiram treatment. Loss of fat tissue and an increase in liver fenestrations were also observed in rats on disulfiram. Given the potent anti-obesogenic effects in rodents, repurposing disulfiram in the clinic could represent a new strategy to treat obesity and its metabolic comorbidities.
Subject(s)
Anti-Obesity Agents/pharmacology , Body Weight/drug effects , Disulfiram/pharmacology , Obesity/drug therapy , Animals , Diet/adverse effects , Female , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Obesity/chemically induced , Obesity/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
The objective of this study was to investigate the effects of cryopreservation on the components of articular cartilage (AC) matrix by utilizing magnetic resonance imaging (MRI) and biochemical assessments. Porcine AC (10mm osteochondral dowels) was collected into four groups - (1) phosphate buffered saline (PBS) control, (2) PBS snap frozen in liquid nitrogen, (3) slow-cooled in dimethyl sulfoxide (DMSO), and (4) slow cooled in PBS (in absence of DMSO). MRI results demonstrated three distinct zones in the cartilage. After exposure to ice formation during cryopreservation procedures, alterations in MRI determined matrix fixed charged density and magnetization transfer rate were noted. In addition, biochemical assays demonstrated significant alterations in chondroitin sulfate and hydroxyproline content over time without differences in hydration or DNA content. In conclusion, MRI was able to detect some changes in the intact cartilage matrix structure consistent with biochemical assessments after ice formation during cryopreservation of intact porcine AC. Furthermore, biochemical assessments supported some of these findings and changed significantly after incubating the cartilage matrix for 36-72 h in PBS in terms of chondroitin sulfate and hydroxyproline content.