Obesity is becoming a pandemic and percutaneous electrical stimulation (PENS) of dermatome T6 has been demonstrated to reduce stomach motility and appetite, allowing greater weight loss than isolated hypocaloric diets. However, modulation of intestinal microbiota could improve this effect and control cardiovascular risk factors. Our objective was to test whether addition of probiotics could improve weight loss and cardiovascular risk factors in obese subjects after PENS and a hypocaloric diet. A pilot prospective study was performed in patients (n = 20) with a body mass index (BMI) > 30 kg/m². Half of them underwent ten weeks of PENS in conjunction with a hypocaloric diet (PENS-Diet), and the other half was treated with a PENS-Diet plus multistrain probiotics (L. plantarum LP115, B. brevis B3, and L. acidophilus LA14) administration. Fecal samples were obtained before and after interventions. The weight loss and changes in blood pressure, glycemic and lipid profile, and in gut microbiota were investigated. Weight loss was significantly higher (16.2 vs. 11.1 kg, p = 0.022), whereas glycated hemoglobin and triglycerides were lower (−0.46 vs. −0.05%, p = 0.032, and −47.0 vs. −8.5 mg/dL, p = 0.002, respectively) in patients receiving PENS-Diet + probiotics compared with those with a PENS-Diet. Moreover, an enrichment of anti-obesogenic bacteria, including Bifidobacterium spp, Akkermansia spp, Prevotella spp, and the attenuation of the Firmicutes/Bacteroidetes ratio were noted in fecal samples after probiotics administration. In obese patients, the addition of probiotics to a PENS intervention under a hypocaloric diet could further improve weight loss and glycemic and lipid profile in parallel to the amelioration of gut dysbiosis.

Type-2 diabetes (T2DM) and arterial hypertension (HTN) are major risk factors for heart failure. Importantly, these pathologies could induce synergetic alterations in the heart, and the discovery of key common molecular signaling may suggest new targets for therapy. Intraoperative cardiac biopsies were obtained from patients with coronary heart disease and preserved systolic function, with or without HTN and/or T2DM, who underwent coronary artery bypass grafting (CABG). Control (n = 5), HTN (n = 7), and HTN + T2DM (n = 7) samples were analysed by proteomics and bioinformatics. Additionally, cultured rat cardiomyocytes were used for the analysis (protein level and activation, mRNA expression, and bioenergetic performance) of key molecular mediators under stimulation of main components of HTN and T2DM (high glucose and/or fatty acids and angiotensin-II). As results, in cardiac biopsies, we found significant alterations of 677 proteins and after filtering for non-cardiac factors, 529 and 41 were changed in HTN-T2DM and in HTN subjects, respectively, against the control. Interestingly, 81% of proteins in HTN-T2DM were distinct from HTN, while 95% from HTN were common with HTN-T2DM. In addition, 78 factors were differentially expressed in HTN-T2DM against HTN, predominantly downregulated proteins of mitochondrial respiration and lipid oxidation. Bioinformatic analyses suggested the implication of mTOR signaling and reduction of AMPK and PPARα activation, and regulation of PGC1α, fatty acid oxidation, and oxidative phosphorylation. In cultured cardiomyocytes, an excess of the palmitate activated mTORC1 complex and subsequent attenuation of PGC1α-PPARα transcription of β-oxidation and mitochondrial electron chain factors affect mitochondrial/glycolytic ATP synthesis. Silencing of PGC1α further reduced total ATP and both mitochondrial and glycolytic ATP. Thus, the coexistence of HTN and T2DM induced higher alterations in cardiac proteins than HTN. HTN-T2DM subjects exhibited a marked downregulation of mitochondrial respiration and lipid metabolism and the mTORC1-PGC1α-PPARα axis might account as a target for therapeutical strategies.

The intestine plays critical roles in nutrient homeostasis and systemic health. The small intestine is the major organ that packages dietary lipids into chylomicrons and secretes them into the mesenteric lymph. Extracellular vesicles (EVs) as a mechanism for cell‐to‐cell communication often exhibit organ specific characteristics. EV secretion from the intestine into the mesenteric lymph—a unique biofluid—remains unexplored. To characterize gut‐derived EVs, Sprague‐Dawley rats were surgically implanted with cannula in the mesenteric lymph duct (for lymph collection) and the duodenum (for lipid infusion). Lymph fluid was collected for assessment of EV secretion. EVs in lymph fluids collected before and after lipid infusion were characterized by transmission electron microscopy, nanoparticle tracking analysis, and further analyzed by flow cytometry with antibodies against CD63, CD81, CD9 and apolipoprotein B (ApoB). Lipid infusion increased lymph triglyceride output peaking at 2 h. Lymph fluids contained EVs with diameters in the range of 20 to 300 nm and the signals of specific EV markers CD63, CD81 and CD9 were significantly elevated following lipid infusion. Depletion of chylomicrons from lymph had differential effects on the percentage and intensity of CD63, CD81 and CD9. In addition, these EVs exhibited distinct patterns in ApoB ⁺ particle population, with the median fluorescence intensity of CD63 and CD81 being significantly higher than that of CD9. To conclude, EVs secreted into the mesenteric lymph could rapidly respond to lipid supply. EVs may bind to and co‐secrete with chylomicrons. Finally, gut‐derived EVs during active lipid absorption may include multiple subtypes with different affinities to chylomicrons. Collectively, these findings highlight the intestine as an EV secretion organ and the mesenteric lymph as an important biofluid harboring EVs, which opens a new venue for future investigation of biological functions of gut‐derived EVs.