Influence of adenovirus 36 seropositivity on the expression of adipogenic microRNAs in obese subjects.

BACKGROUND: Infection by Adenovirus 36 (Ad-36) has been associated with adipogenesis using cell and animal models, and a high risk of developing obesity has been reported in Ad-36-seropositive individuals. However, molecular mechanisms involved in the maintenance over the years of adipogenesis associated with Ad-36 has not been investigated in human adipose tissue. Epigenetic mechanisms, such as micro-RNAs (miRNAs) that regulate gene expression at the post-transcriptional level, have shown an important role in the development and maintenance of metabolic diseases. AIM: This study investigated the expression of miRNA associated with the adipogenic process in visceral adipose tissue from obese individuals according to Ad-36 serology. METHODS: Obese individuals were separated according to their status of Ad-36 serology in seropositive (Ad-36 (+); n = 29) and seronegative (Ad-36 (-); n = 28) groups. Additionally, a group of lean controls (n = 17) was selected to compare with obese individuals. Biopsies of visceral adipose tissue were obtained to evaluate miRNA and gene expression. The study of Ad-36 serology was carried out by ELISA. The expression of pro-adipogenic (miR-17 and miR-210) and anti-adipogenic (miR-155, miR-130 and miR-27a) miRNAs was evaluated using Taqman advanced miRNA assays by qPCR. The expression of adipogenes encoding LEP, ADIPOQ, and PPARγ was evaluated by Taqman predesigned assays through qPCR. RESULTS: The obese group had higher LEP (p < 0.001) and PPARγ (p = 0.016) expression and lower ADIPOQ expression (p = 0.017), and also had higher expression of miR-210 (p = 0.039), whereas lower expression of miR-155 (p = 0.019) and miR-27a (p = 0.028) as compared to lean controls. Higher PPARγ expression (p = 0.008), but no influence on LEP or ADIPOQ expression was observed in Ad-36 (+) group. Those seropositive individuals also had higher expression of the miR-17 (p = 0.028) and lower levels of miR-155 (p = 0.031) in adipose tissue as compared to seronegative subjects. CONCLUSIONS: Individuals with previous infection by Ad-36 had higher expression of the pro-adipogenic miR-17 and lower expression of the anti-adipogenic miR-155, which could lead to an increased adipogenic status by positively modulating PPARγ expression in adipose tissue from obese subjects.

Bariatric surgery in HIV patients: experience of an Obesity Reference Center in France.

BACKGROUND: Few data on bariatric surgery are available regarding obese human immunodeficiency virus (HIV)-infected patients. SETTINGS: Antoine Beclere hospital, Clamart, Paris-sud University, France METHODS: Prospective observational follow-up study recruited HIV-infected patients who underwent bariatric surgery from 2009 to 2015. Baseline demographic characteristics, surgery characteristics, perioperative outcomes, changes in weight loss, HIV markers, antiretroviral drug plasma levels are described. RESULTS: There were 10 patients followed before and after sleeve gastrectomy: 2 men and 8 women; 50% of African origin; median age, 48.5 years, median time since HIV infection, 7.5 years; median body mass index, 48.5 kg/m2. Of patients, 8 had co-morbidities. All except 2 patients received antiretroviral drugs at the time of surgery with a median CD4 cell count at 709/mm3. There was no death or postoperative infectious complications. The median follow-up was 18 months (range, 15-55). The median postoperative weight loss was 43 kg (range, 17-83). Median percentage of excess weight loss was 82.5% (range, 35-119) at the latest visit after surgery. All co-morbidities were resolutive with weight loss. We observed no significant modification of CD4 cell count before and after surgery. Pharmacokinetics of antiretroviral drugs remains adequate and efficacious. CONCLUSION: Our prospective series is the largest one on sleeve gastrectomy procedures performed on obese-treated HIV-infected patients. The sleeve generates good results in weight loss, with no significant impact on HIV infection, and with improvement of obesity-associated co-morbidities. Optimal management of HIV-infected patients with morbid obesity may include classical surgical procedures.

Long-term virologic outcomes following bariatric surgery in patients with HIV.

The management of morbid obesity and its metabolic complications among HIV-infected patients requires a multi-disciplinary approach, with surgical interventions as one option. We sought to assess the long-term durability of ART among HIV-infected patients undergoing bariatric procedures for the management of morbid obesity. During the study period, 7 patients underwent a bariatric surgery procedure for the management of morbid obesity: 3 patients underwent sleeve gastrectomy, 2 patients underwent laparoscopic banding, and 2 patients underwent Roux-en-Y gastric bypass surgery. Overall, the proportion of undetectable HIV viral load levels did not change after the bariatric procedures, although 2 patients did require temporary cessation of medications due to procedure-related complications. Sleeve gastrectomy and Roux-en-Y gastric bypass were safe and effective among morbidly obese HIV-infected patients in our clinic population.

Alteration of the leptin network in late morbid obesity induced in mice by brain infection with canine distemper virus.

Viruses can induce progressive neurologic disorders associated with diverse pathological manifestations, and therefore, viral infection of the brain can impair differentiated neural functions, depending on the initial viral tropism. We have previously reported that canine distemper virus (CDV) targets certain mouse brain structures, including the hypothalamus, early and selectively. Infected mice exhibit acute encephalitis, with late disease, characterized by motor impairment or obesity syndrome, appearing in some of the surviving mice several months after the initial viral replication. In the present study, we show viral persistence in the hypothalami of obese mice, as demonstrated by low, but still significant, levels of CDV nucleoprotein transcripts, associated with a dramatic decrease in F gene mRNAs. Given the pivotal role of the hypothalamus in obesity (eating behavior, energy consumption, and neuroendocrine function) and that of leptin, the adipose tissue-derived satiety factor acting through hypothalamic receptors, we analyzed the leptin networks in both obese and nonobese mice. The discrepancy found between the chronic and dramatic increase in blood leptin levels and the occurrence of obesity may be due to leptin resistance in the brain. In fact, expression of the long leptin receptor isoform, representing the functional leptin receptor, was specifically downregulated in the hypothalami of obese mice, explaining their inability to generate an adequate response to leptin in the brain. Intriguingly, during the acute phase of infection, its expression was increased in CDV-targeted structures in all infected mice and remained high in obese mice in all CDV-targeted structures, except for the hypothalamus. The biphasic change in hypothalamic leptin receptor expression seen during the progression of CDV-induced obesity provides a new paradigm for understanding mechanisms of neuroendocrinological, virus-induced abnormalities.