Publications

The small intestine has an underappreciated role as a lipid storage organ. Under conditions of high dietary fat intake, enterocytes can minimize the extent of postprandial lipemia by storing newly absorbed dietary fat in cytoplasmic lipid droplets. Lipid droplets can be subsequently mobilized for the production of chylomicrons. The mechanisms that regulate this process are poorly understood. We report here that the milk protein Mfge8 regulates hydrolysis of cytoplasmic lipid droplets in enterocytes after interacting with the αvβ3 and αvβ5 integrins. Mice deficient in Mfge8 or the αvβ3 and αvβ5 integrins accumulate excess cytoplasmic lipid droplets after a fat challenge. Mechanistically, interruption of the Mfge8-integrin axis leads to impaired enterocyte intracellular triglyceride hydrolase activity in vitro and in vivo. Furthermore, Mfge8 increases triglyceride hydrolase activity through a PI3 kinase/mTORC2-dependent signaling pathway. These data identify a key role for Mfge8 and the αvβ3 and αvβ5 integrins in regulating enterocyte lipid processing.

A 39-year-old male ex-smoker gave a history of exertional chest pain ever since he suffered a respiratory tract infection. Clinical examination, electrocardiogram and echocardiography were normal and he was referred for a cardiac CT scan to assess coronary artery calcification and patency. The scan demonstrated incidental fistulae between the right internal mammary artery and the right coronary artery, and the left internal mammary artery and the left anterior descending artery.

PURPOSE

The primary objective of this study was to analyze the relationships between bone microstructure and strength, and male osteoporosis risk factors including age, body mass index, serum 25-hydroxyvitamin D level, and testosterone level. A secondary objective was to compare microstructural and strength parameters between men with normal, low, and osteoporosis-range areal bone mineral density (aBMD).

METHODS

Seventy-eight healthy male volunteers (mean age 62.4 ± 7.8 years, range 50-84 years) were recruited. The participants underwent dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of the ultra-distal radius and tibia. From the HR-pQCT images, volumetric bone mineral density (BMD) and cortical and trabecular bone microstructure were evaluated, and bone strength and cortical load fraction (Ct.LF) were estimated using micro-finite element analysis (μFEA).

RESULTS

Age was more strongly correlated with bone microstructure than other risk factors. Age had significant positive correlations with cortical porosity at both ultra-distal radius and tibia ( = 0.36,  = 0.001, and  = 0.47,  < 0.001, respectively). At the tibia, age was negatively correlated with cortical BMD, whereas it was positively correlated with trabecular BMD. In μFEA, age was negatively correlated with Ct.LF, although not with bone strength. Compared with men with normal aBMD, men with low or osteoporosis-range aBMD had significantly poor trabecular bone microstructure and lower bone strength at the both sites, while there was no significant difference in cortical bone.

CONCLUSIONS

Cortical bone microstructure was negatively affected by aging, and there was a suggestion that the influence of aging may be particularly important at the weight-bearing sites.