👤 Kelsey E Jarrett

The chimeric cytokine IC7Fc conveys the metabolic signaling properties of the glycoprotein 130 receptor cytokines interleukin-6 and ciliary neurotrophic factor via membrane-bound signaling. IC7Fc was previously shown to slow the progression of type 2 diabetes mellitus, and here, we demonstrate its effect on atherosclerotic development. In APOE*3-Leiden.CETP mice, an atherosclerosis-prone model with a humanized lipoprotein metabolism, IC7Fc markedly lowered plasma triglyceride and total cholesterol levels. This was mechanistically explained by an inhibition of de novo lipogenesis in the liver, increased synthesis of bile acids from cholesterol, and down-regulated apolipoprotein B synthesis, which resulted in decreased cholesterol secretion in very low-density lipoprotein particles. As a consequence, IC7Fc treatment considerably reduced atherosclerotic lesion formation and vascular inflammation compared with current antihyperlipidemic therapy. In conclusion, IC7Fc is a promising pharmacological treatment for cardiometabolic diseases targeting hyperlipidemia and inflammation. Show less

Patients with lipoprotein lipase (LPL) deficiency, an inherited disorder, develop hypertriglyceridemia, which can lead to recurrent pancreatitis. The mainstay of therapy is medical nutritional therapy. We present the case of a 35-year-old woman with LPL deficiency who experienced recurrent hospitalizations for hypertriglyceridemia-induced pancreatitis, which was effectively treated with orlistat. Other agents that have been studied for the treatment of LPL deficiency are costly and have limiting side effects. Studies have shown orlistat to be safe and effective for the treatment of LPL deficiency in children. No studies have been performed in adults with LPL deficiency. Orlistat may be a potential adjunctive treatment option for LPL deficiency in adults, given its availability and favorable safety profile. Further research regarding orlistat in the setting of LPL deficiency is needed. Show less

The basic-helix-loop-helix transcription factor HeyL is expressed at high levels by neural crest progenitor cells (NCPs) that give rise to neurons and glia in dorsal root ganglia (DRG). Since HeyL expression was observed in these NCPs during the period of neurogenesis, we generated HeyL null mutants to help examine the factor's role in ganglion neuronal specification. Homozygous null mutation of HeyL reduced the number of TrkC(+) neurons in DRG at birth including the subpopulation that expresses the ETS transcription factor ER81. Conversely, null mutation of the Hey paralog, Hey1, increased the number of TrkC(+) neurons. Null mutation of HeyL increased expression of the Hey paralogs Hey1 and Hey2, suggesting that HeyL normally inhibits their expression. Double null mutation of both Hey1 and HeyL rescued TrkC(+) neuron numbers to control levels. Thus, the balance between HeyL and Hey1 expression regulates the differentiation of a subpopulation of TrkC(+) neurons in the DRG. Show less