Lipid-engorged macrophages accumulate in atherosclerotic plaques where chronic inflammation ensues. Moore and colleagues show that macrophage migration to chemokines and egress is arrested by netrin-1, which is secreted in the plaque lesions. Atherosclerotic plaque formation is fueled by the persistence of lipid-laden macrophages in the artery wall. The mechanisms by which these cells become trapped, thereby establishing chronic inflammation, remain unknown. Here we found that netrin-1, a neuroimmune guidance cue, was secreted by macrophages in human and mouse atheroma, where it inactivated the migration of macrophages toward chemokines linked to their egress from plaques. Acting via its receptor, UNC5b, netrin-1 inhibited the migration of macrophages directed by the chemokines CCL2 and CCL19, activation of the actin-remodeling GTPase Rac1 and actin polymerization. Targeted deletion of netrin-1 in macrophages resulted in much less atherosclerosis in mice deficient in the receptor for low-density lipoprotein and promoted the emigration of macrophages from plaques. Thus, netrin-1 promoted atherosclerosis by retaining macrophages in the artery wall. Our results establish a causative role for negative regulators of leukocyte migration in chronic inflammation.

Butyrate is physiologically produced by the microbial fermentation of dietary fibers and plays a plurifunctional role in intestinal cells. This review examines the recent findings regarding the role and mechanisms by which butyrate regulates intestinal metabolism and discusses how these findings could improve the treatment of several gastrointestinal disorders. Butyrate is more than a primary nutrient that provides energy to colonocytes and acts as a cellular mediator in those cells through several mechanisms. One remarkable property of butyrate is its ability to inhibit histone deacetylases, which is associated with the direct effects of butyrate and results in gene regulation, immune modulation, cancer suppression, cell differentiation, intestinal barrier regulation, oxidative stress reduction, diarrhea control, visceral sensitivity and intestinal motility modulation. All of these actions make butyrate an important factor for the maintenance of gut health. From studies published over 30 years, there is no doubt of the important role that butyrate plays in maintaining intestinal homeostasis. However, despite these effects, clinical studies are still required to validate the routine use of butyrate in clinical practice and, specifically, in the treatment of intestinal diseases.

The number of adolescent and adult patients submitting to bariatric surgery is increasing rapidly around the world. This review describes the literature published in the last few years concerning nutritional deficiencies after bariatric surgery as well as their etiology, incidence, treatment and prevention. Although bariatric surgery was first introduced in the 1950s, safe and successful surgical management has progressed over the last two decades and longer post-surgical follow-up data are now available. Most of the patients undergoing malabsorptive procedures will develop some nutritional deficiency, justifying mineral and multivitamin supplementation to all postoperatively. Nutrient deficiency is proportional to the length of absorptive area and to the percentage of weight loss. Low levels of iron, vitamin B12, vitamin D and calcium are predominant after Roux-en-Y gastric bypass. Protein and fat-soluble vitamin deficiencies are mainly detected after biliopancreatic diversion. Thiamine deficiency is common in patients with frequent vomiting. As the incidence of these deficiencies progresses with time, the patients should be monitored frequently and regularly to prevent malnutrition. Nutritional deficiencies can be prevented if a multidisciplinary team regularly assists the patient. Malnutrition is generally reverted with nutrient supplementation, once it is promptly diagnosed. Especial attention should be given to adolescents, mainly girls at reproductive age who have a substantial risk of developing iron deficiency. Future studies are necessary to detect nutrient abnormalities after new procedures and to evaluate the safety of bariatric surgery in younger obese patients.

Objective— The scavenger receptors SR-A and CD36 have been implicated in macrophage foam cell formation during atherogenesis and in the regulation of inflammatory signaling pathways, including those leading to lesional macrophage apoptosis and plaque necrosis. To test the impact of deleting these receptors, we generated Apoe ^−/− mice lacking both SR-A and CD36 and fed them a Western diet for 12 weeks. Methods and Results— We analyzed atheroma in mice, assessing lesion size, foam cell formation, inflammatory gene expression, apoptosis, and necrotic core formation. Aortic root atherosclerosis in Apoe ^−/− Cd36 ^−/− Msr1 ^−/− mice, as assessed by morphometry, electron microscopy, and immunohistochemistry, showed no decrease in lesion area or in vivo foam cell formation when compared to Apoe ^−/− mice. However, Apoe ^−/− Cd36 ^−/− Msr1 ^−/− lesions showed reduced expression of inflammatory genes and morphological analysis revealed a ≈30% decrease in macrophage apoptosis and a striking ≈50% decrease in plaque necrosis in aortic root lesions of these mice. Conclusions— Although targeted deletion of SR-A and CD36 does not abrogate macrophage foam cell formation or substantially reduce atherosclerotic lesion area in Apoe ^−/− mice, loss of these pathways does reduce progression to more advanced necrotic lesions. These data suggest that targeted inhibition of these pathways in vivo may reduce lesional inflammation and promote plaque stability.