Lipoprotein Lipase Overexpression in Skeletal Muscle Attenuates Weight Regain by Potentiating Energy Expenditure

Moderate weight loss improves numerous risk factors for cardiometabolic disease; however, long-term weight loss maintenance (WLM) is often thwarted by metabolic adaptations that suppress energy expenditure and facilitate weight regain. Skeletal muscle has a prominent role in energy homeostasis; therefore, we investigated the effect of WLM and weight regain on skeletal muscle in rodents. In skeletal muscle of obesity-prone rats, WLM reduced fat oxidative capacity and downregulated genes involved in fat metabolism. Interestingly, even after weight was regained, genes involved in fat metabolism were also reduced. We then subjected mice with skeletal muscle lipoprotein lipase overexpression (mCK-hLPL), which augments fat metabolism, to WLM and weight regain and found that mCK-hLPL attenuates weight regain by potentiating energy expenditure. Irrespective of genotype, weight regain suppressed dietary fat oxidation and downregulated genes involved in fat metabolism in skeletal muscle. However, mCK-hLPL mice oxidized more fat throughout weight regain and had greater expression of genes involved in fat metabolism and lower expression of genes involved in carbohydrate metabolism during WLM and regain. In summary, these results suggest that skeletal muscle fat oxidation is reduced during WLM and regain, and therapies that improve skeletal muscle fat metabolism may attenuate rapid weight regain.     

Neurofibromatosis Type 1 Diagnosed in a Child Based on Multiple Juvenile Xanthogranulomas and Juvenile Myelomonocytic Leukemia

An association between juvenile xanthogranuloma (JXG), neurofibromatosis type 1 (NF1), and juvenile myelomonocytic leukemia (JMML) has been described in the literature but has only been documented in approximately 20 cases. We diagnosed a patient with NF1 at 25 months of age, before any cutaneous stigmata of this disease had appeared, because we decided to screen for the NF1 gene mutation because of his presentation with multiple JXGs and moderate macrocephaly (2.5 standard deviations) at 9 months of age and JMML diagnosed at 20 months of age. The child is well today after treatment with chemotherapy and allogenic bone marrow transplantation. With increased awareness, patients with JXG and NF1 who develop symptoms possibly related to JMML, such as paleness, skin bleeding, cough, unexplained fever, and hepatosplenomegaly, should be further evaluated. We also emphasize that multiple JXG lesions can be an early marker of NF1.