Hepatic Vagotomy in Patients With Obesity Leads to Improvement of the Cholesterol to High-Density Lipoprotein Ratio.

INTRODUCTION/PURPOSE: The obesity epidemic is rapidly growing, and visceral adiposity is associated with metabolic consequences secondary to peroxisome proliferator-activated receptor (PPAR)-induced inter-organ signaling pathways. PPARs are ligand-activated transcription factors that modulate vagal pathways which can improve blood pressure, arterial remodeling, cholesterol levels, and insulin sensitivity. However, an obesity-induced inflammatory milieu can interfere with the beneficial effects of PPAR activity, suggesting that a dysregulated PPAR-vagus pathway may play a role in the pathogenesis of obesity-related hypertension. Therefore, we hypothesized that hepatic vagotomy (HV) in patients with obesity would result in a significant reduction in blood pressure and/or the number of hypertension medications compared to control. METHODS: We conducted a retrospective chart review of 160 patients undergoing laparoscopic sleeve gastrectomy. Patients were divided into HV and control groups, and information was collected at each clinic visit. RESULTS: At six-months post-operation, the HV group was found to have significantly lower total cholesterol (TC)/high-density lipoprotein (HDL) ratios than the control group. The HV group also had a numerically better blood profile for TC, HDL, low-density lipoprotein (LDL), triglycerides, C-reactive protein, and LDL/HDL ratio. Hypertensive patients in the HV group showed numerically lower hypertension medication counts after six weeks when compared to control. CONCLUSION: We present the first study to report clinically significant changes related to HV in human subjects. Our results did not support our initial hypothesis but did demonstrate an improvement of the TC/HDL ratio with HV in patients with obesity. Future studies should confirm these findings in a randomized control trial.

Chronic Binge Alcohol and Ovarian Hormone Loss Dysregulate Circulating Immune Cell SIV Co-Receptor Expression and Mitochondrial Homeostasis in SIV-Infected Rhesus Macaques.

Effective antiretroviral therapy (ART) has transitioned HIV to a chronic disease, with more than 50% of people living with HIV (PLWH) being over the age of 50. HIV targets activated CD4+ T cells expressing HIV-specific co-receptors (CCR5 and CXCR4). Previously, we reported that chronic binge alcohol (CBA)-administered male rhesus macaques had a higher percentage of gut CD4+ T cells expressing simian immunodeficiency virus (SIV) co-receptor CXCR4. Evidence also suggests that gonadal hormone loss increased activated peripheral T cells. Further, mitochondrial function is critical for HIV replication and alcohol dysregulates mitochondrial homeostasis. Hence, we tested the hypothesis that CBA and ovariectomy (OVX) increase circulating activated CD4+ T cells expressing SIV co-receptors and dysregulate mitochondrial homeostasis in SIV-infected female rhesus macaques. Results showed that at the study end-point, CBA/SHAM animals had increased peripheral CD4+ T cell SIV co-receptor expression, and a lower CD4+ T cell count compared to CBA/OVX animals. CBA and OVX animals had altered peripheral immune cell gene expression important for maintaining mitochondrial homeostasis. These results provide insights into how at-risk alcohol use could potentially impact viral expression in cellular reservoirs, particularly in SIV-infected ovariectomized rhesus macaques.