1. Investigación

Periodontitis is a chronic inflammatory disease of the periodontium, or the supportive tissues around the tooth. This disease has been related to different risk factors, such as the presence of plaque and calculus, tobacco smoking, low socioeconomic status, and the immune state of the host. Importantly, the chronic inflammatory environment generated by periodontitis may lead to tooth loss and diverse systemic complications, such as cardiovascular disease, osteoarthritis and metabolic disease. Recent investigations have supported the role of obesity as a risk factor for periodontitis. Furthermore, studies have found obesity to compromise healing after periodontal therapy; however, the mechanisms underlying this association are not well understood. Proteins called 'adipokines' could be the factor linking obesity to periodontitis. Adipokines are bioactive molecules with hormonal properties and a structure similar to cytokines produced by the adipose tissue. Although adipokines have both pro- and anti-inflammatory effects, the shift towards pro-inflammatory actions occurs when the adipose tissue becomes pathological, as observe in the progression of conditions such as obesity or adiposopathy. This article reviews the role of adipokines in the pathophysiology and progression of periodontitis by focusing on their impact on inflammation and the molecular mechanisms through which adipokines contribute to the onset and development of periodontitis.

Longevity has been a topic of interest since the beginnings of humanity, yet its aetiology and precise mechanisms remain to be elucidated. Aging is currently viewed as a physiological phenomenon characterized by the gradual degeneration of organic physiology and morphology due to the passage of time where both external and internal stimuli intervene. The influence of intrinsic factors, such as progressive telomere shortening, genome instability due to mutation buildup, the direct or indirect actions of age-related genes, and marked changes in epigenetic, metabolic, and mitochondrial patterns constitute a big part of its underlying endogenous mechanisms. On the other hand, several psychosocial and demographic factors, such as diet, physical activity, smoking, and drinking habits, may have an even more significant impact on shaping the aging process. Consequentially, implementing dietary and exercise patterns has been proposed as the most viable alternative strategy for attenuating the most typical degenerative aging changes, thus increasing the likelihood of prolonging lifespan and achieving successful aging.

Inflammation is a common factor of pathologies such as obesity, type 2 diabetes or neurodegenerative diseases. Chronic inflammation is considered part of the pathogenic mechanisms of different disorders associated with aging. Interestingly, peripheral inflammation and the associated metabolic alterations not only facilitate insulin resistance and diabetes but also neurodegenerative disorders. Therefore, the identification of novel pathways, common to the development of these diseases, which modulate the immune response and signaling is key. It will provide highly relevant information to advance our knowledge of the multifactorial process of aging, and to establish new biomarkers and/or therapeutic targets to counteract the underlying chronic inflammatory processes. One novel pathway that regulates peripheral and central immune responses is triggered by the cytokines pleiotrophin (PTN) and midkine (MK), which bind its receptor, Receptor Protein Tyrosine Phosphatase (RPTP) b/z, and inactivate its phosphatase activity. In this review, we compile a growing body of knowledge suggesting that PTN and MK modulate the immune response and/or inflammation in different pathologies characterized by peripheral inflammation associated with insulin resistance, such as aging, and in central disorders characterized by overt neuroinflammation, such as neurodegenerative diseases and endotoxemia. Evidence strongly suggests that regulation of the PTN and MK signaling pathways may provide new therapeutic opportunities particularly in those neurological disorders characterized by increased PTN and/or MK cerebral levels and neuroinflammation. Importantly, we discuss existing therapeutics, and others being developed, that modulate these signaling pathways, and their potential use in pathologies characterized by overt neuroinflammation.

Overweight and obesity amongst childhood are currently global health issues. However, this is the best stage of life to prevent diseases and to promote healthy habits. In our study, we evaluate the effectiveness of the THAO Salud Infantil, a community-based intervention program, by means of a cross-sectional study carried out from 2009 to 2019 surveying children aged 3 to 12 years old (n = 27,686). During the study timeframe, overweight and obesity prevalence, according to both the International Obesity Task Force and Orbegozo Foundation criteria, showed a downward trend. Differences in the anthropometric variables were observed from the beginning to the end of the study, mainly in girls. Analysis of the influence of the socioeconomic status revealed that children from families with lower incomes are in greater risk of suffering from overweight and obesity and showed lower effectiveness of the actions proposed by the program. The overall results of the study confirmed the effectiveness of community-based interventions in terms of childhood overweight/obesity prevention.

Introduction:Online interventions have long been shown to be an e􀀀ectivemeans to promote a healthy lifestyle, thereby helping to control body weight and blood pressure figures. Likewise, using video modeling is also considered an e􀀀ective way to guide patients through behavioral interventions. Nonetheless, to the best of our knowledge, this study is the first to analyze how the presence of patients’ “own doctor” in the audiovisual content of a web-based lifestyle program (“Living Better”) aimed at promoting regular physical exercise and healthy eating behavior, compared with an “unknown doctor,” influences the outcomes of adults with obesity and hypertension. Materials and methods: A total of 132 patients were randomly assigned either to the experimental (n = 70) or control (n = 62) group (“own doctor” or “unknown doctor”, respectively). The body mass index, systolic and diastolic blood pressure, number of antihypertensive drugs used, physical activity level, and quality of life was assessed and compared at baseline and post-intervention (12 weeks). Results: The intention-to-treat analysis showed intragroup significant improvements in both groups in terms of the body mass index (control group: mean di􀀀erence −0.3, 95% CI [−0.5, −0.1], p = 0.002; experimental group: −0.4 [−0.6, −0.2], p < 0.001) and systolic blood pressure (control group: −2.3 [−4.4, −0.2], p = 0.029; experimental group: −3.6 [−5.5, −1.6], p< 0.001). In addition, there were also significant improvements in the experimental group for the diastolic blood pressure (−2.5 [−3.7, −1.2], p < 0.001), physical activity (479 [9, 949], p = 0.046), and quality of life (5.2 [2.3, 8.2], p = 0.001). However, when comparing the experimental with the control group, no between-group significant di􀀀erences were found in these variables. Conclusions: This study suggests that the presence of patients’ “own doctor” in the audiovisual content of a web-based intervention, aimed at promoting a healthy lifestyle among adults with obesity and hypertension, do not show significant additional benefits over the e cacy of e–counseling.

Background: The ‘Living Better’ web-based programme has shown short- and long-term benefits for body composition and psychological variables in obese patients with hypertension by promoting a healthier lifestyle. To further explore the potential of this programme, in this work we aimed to explore the possible effect of the patient’s ‘own doctor’ appearing in the video content of the Living Better intervention. (2) Methods: A total of 132 patients were randomly assigned either to the experimental (EG, n = 70) or control (CG, n = 62) group (with a doctor the patient knew as ‘their own’ or an ‘unknown doctor’, respectively). The body mass index (BMI), motivation towards physical activity (PA), PA levels, motivation to change one’s eating habits, adherence to the Mediterranean diet, and eating behaviour were all assessed and compared at baseline and post-intervention (12 weeks). (3) Results: The results of this study confirmed the positive effects of the Living Better programme on BMI and external eating style, with significant improvements in these variables in both groups. In addition, in the EG there was higher intrinsic motivation to change eating behaviour (mean difference of 0.9, 95% CI [0.1, 1.6], p = 0.032) and lower amotivation (mean difference of −0.6, 95% CI [−1.2, −0.1], p = 0.027) compared to the CG. (4) Conclusions: This study suggests that the presence of the patients’ own doctor in the audiovisual content of the Living Better intervention did not have significant additional benefits in terms of BMI or external eating style. However, their presence did improve intrinsic motivation and amotivation related to eating habits.

The aim of this study was to evaluate the effect of Compound 21 (C21), a selective AT2R agonist, on the prevention of endothelial dysfunction, extracellular matrix (ECM) remodeling and arterial stiffness associated with diet-induced obesity (DIO). 5-week-old male C57BL/6J mice were fed a standard (Chow) or high-fat diet (HF) for 6 weeks.Half of the animals of each group were simultaneously treated with C21 (1mg/kg/day, in the drinking water), generating 4 groups: Chow C, Chow C21, HF C, HF C21. Vascular function and mechanical properties were determined in the abdominal aorta. To evaluate ECM remodeling, collagen deposition, activity of metalloproteinases (MMP) 2 and 9 and TGF-1 concentration were analyzed in the plasma. Abdominal aortas from HF C mice showed endothelial dysfunction as well as enhanced contractile but reduced relaxant responses to Ang II.This effect was abrogated with C21 treatment by preserving NO availability. A left-shift inthe tension-stretch relationship, paralleled by an augmented β-index (marker of intrinsic arterial stiffness), and enhanced collagen deposition and MMP-2/-9 activities were also detected in HF mice. However, when treated with C21, HF mice exhibited lower TGF-1 levels in abdominal aortas together with reduced MMP activities and collagen deposition compared with HF C mice. In conclusion, these data demonstrate that AT2R stimulation by C21 in obesity preserves NO availability and prevents unhealthy vascular remodeling, thus protecting the abdominal aorta in HF mice against the development of endothelial dysfunction, ECM remodeling and arterial stiffness.

Dietary treatment with high-fat diets (HFD) triggeenrs diabetes and hyperleptinemia, con- comitantly with a partial state of leptin resistance that affects hepatic and adipose tissue but not the heart. In this context, characterized by widespread steatosis, cardiac lipid con- tent remains unchanged. As previously reported, HFD-evoked hyperleptinemia could be a pivotal element contributing to increase fatty-acid (FA) metabolism in the heart and to prevent cardiac steatosis. This metabolic adaptation might theoretically reduce energy efficiency in cardiomyocytes and lead to cardiac electrophysiological remodeling. There- fore the aim of the current study has been to investigate the impact of long-term HFD on cardiac metabolism and electrophysiological properties of the principal ionic currents responsible of the action potential duration in mouse cardiomyocytes. Male C57BL/6J mice were fed a control (10 kcal% from fat) or HFD (45 kcal% from fat) during 32 weeks. Quantification of enzymatic activities regulating mitochondrial uptake of pyruvate and FA showed an increase of both carnitine-palmitoyltransferase and citrate synthase activities together with a decrease of lactate dehydrogenase and pyruvate dehydrogenase activities. Increased expression of uncoupling protein-3, Mn-, and Cu/Zn-superoxide dismutases and catalase were also detected. Total glutathione/oxidized glutathione ratios were unaffected by HFD. These data suggest that HFD triggers adaptive mechanisms aimed at facilitating FA catabolism, and preventing oxidative stress. All these changes did not affect the dura- tion of action potentials in cardiomyocytes and only slightly modified electrocardiographic parameters.

Bariatric surgery (BS) results in sustained weight loss and may reverse inflammation, metabolic alterations, extracellular matrix remodeling and arterial stiffness. We hypothesize that increased stiffening in omental arteries from obese patients might be associated with an increase in MMP activity and a decrease in p-AMPK, together with systemic oxidative stress and inflammation. Moreover, BS could contribute to reversing these alterations. This study was conducted with 38 patients of Caucasian origin: 31 adult patients with morbid obesity (9 men and 22 women; mean age 46 years and BMI = 42.7 1.0 kg/m2) and 7 non-obese subjects (7 women; mean age 45 years and BMI = 22.7 0.6 kg/m2). Seventeen obese patients were studied before and 12 months after BS. The stiffness index b, an index of intrinsic arterial stiffness, was determined in omental arteries and was significantly higher in obese patients. Levels of phosphorylated AMPK (p-AMPKThr􀀀172) and SIRT-1 were significantly lower in peripheral blood mononuclear cells (PBMCs) from obese patients than those from non-obese patients (p < 0.05) and were normalized after BS. Total and active MMP-9 activities, LDH, protein carbonyls and uric acid were higher in obese patients and reduced by BS. Moreover, there was a correlation between plasmatic LDH levels and the stiffness index b. BS has a beneficial effect on abnormal MMP-9, LDH and AMPK activities that might be associated with the development of arterial stiffness in obese patients. Since these parameters are easily measured in blood samples, they could constitute potential biomarkers of cardiovascular risk in morbid obesity

The incidence of obesity and its related disorders has increased dramatically in recent years and has become a pandemic. Adipose tissue is a crucial regulator of these diseases due to its endocrine capacity. Thus, understanding adipose tissue metabolism is essential to finding new effective therapeutic approaches. The “omic” revolution has identified new concepts about the complexity of the signaling pathways involved in the pathophysiology of adipose tissue-associated disorders. Specifically, advances in transcriptomics have allowed its application in clinical practice and primary or secondary prevention. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of adipose tissue since they can modulate gene expression at the epigenetic, transcriptional, and post-transcriptional levels. They interact with DNA, RNA, protein complexes, other noncoding RNAs, and microRNAs to regulate a wide range of physiological and pathological processes. Here, we review the emerging field of lncRNAs, including how they regulate adipose tissue biology, and discuss circulating lncRNAs, which may represent a turning point in the diagnosis and treatment of adipose tissue-associated disorders. We also highlight potential biomarkers of obesity and diabetes that could be considered as therapeutic targets.