Obesity and depression are two of the most prevalent diseases with increasing trends worldwide; it has been some time since the first epidemiological associations were first described. Currently, there is abundant evidence showing the physiology and the molecular aspects that intersect the biology of both ailments. This narrative review aims to synthesize current evidence on the epidemiology and shared pathophysiology of obesity and major depressive disorder, emphasizing convergent inflammatory, neuroendocrine, metabolic, genetic, and gut–brain mechanisms. We aggregate evidence for a bidirectional relationship mediated by: (1) chronic low-grade inflammation (elevated CRP, IL-6, TNF-α; microglial activation); (2) HPA axis dysregulation (hyper/corticosteronemia, impaired feedback, altered CRH/ACTH signaling); (3) metabolic and neurotrophic signaling deficits (insulin and leptin resistance, dysregulated adipokines such as leptin/adiponectin, impaired BDNF and synaptic plasticity); (4) lipid-derived neurotoxicity and mitochondrial stress (saturated fatty acids, ceramides, oxidative stress); and (5) gut–brain axis perturbations (microbiota dysbiosis, increased intestinal permeability, LPS-driven endotoxemia, altered short-chain fatty acids and tryptophan–kynurenine metabolism). We highlight how these convergent pathways promote neuroinflammation and mood dysregulation in individuals with obesity and summarize clinical consequences for screening, integrated management, and targeted interventions that modulate immune, neuroendocrine, metabolic, and microbial processes. Finally, we outline priorities for identifying shared biomarkers and advancing personalized strategies via multi-omics and systems medicine to improve prevention, diagnosis, and treatment.

The study of adipose tissue has received considerable attention due to its importance not just in maintaining body energy homeostasis but also in playing a role in a number of other physiological processes. Beyond storing energy, adipose tissue is important in endocrine, immunological, and neuromodulatory functions, secreting hormones that participate in the regulation of energy homeostasis. An imbalance of these functions will generate structural and functional changes in the adipose tissue, favoring the secretion of deleterious adipocytokines that induce a pro-inflammatory state, allowing the development of metabolic and cardiovascular diseases and even some types of cancer. A common theme worldwide has been the development of professional guidelines for the control and treatment of obesity, with emphasis on hypocaloric diets and exercise. The aim of this review is to examine the pathophysiological mechanisms of obesity, considering the relationship among adipose tissue and two aspects that contribute positively or negatively to keeping a healthy body homeostasis, namely, exercise and noninfectious diseases. We conclude that the relationship of these aspects does not have homogeneous effects among individuals. Nevertheless, it is possible to establish some common mechanisms, like a decrease in pro-inflammatory markers in the case of exercise, and an increase in chronic inflammation in non-communicable diseases. An accurate diagnosis might consider the particular variables of a patient, namely their molecular profile and how it affects its metabolism, routines, and lifestyle; their underling health conditions; and probably even the constitution of their microbiome. We foresee that the development and accessibility of omics approaches and precision medicine will greatly improve the diagnosis, treatment, and successful outcomes for obese patients.

Following our studies on the gastroprotective effect and cytotoxicity of terpene derivatives, new amides were prepared from the diterpene 8(17)-labden-15,19-dioic acid (junicedric acid) and its 8(9)-en isomer with C-protected amino acids (amino acid esters). The new compounds were evaluated for their gastroprotective effect in the ethanol/HCl-induced gastric lesions model in mice, as well as for cytotoxicity using the following human cell lines: normal lung fibroblasts (MRC-5), gastric adenocarcinoma cells (AGS) and liver hepatocellular carcinoma (Hep G2). A dose-response experiment showed that at 25 mg/kg the C-15 leucyl and C-15,19-dileucylester amides of junicedric acid reduced gastric lesions by about 65.6 and 49.6%, respectively, with an effect comparable to lansoprazole at 20 mg/kg (79.3% lesion reduction). The comparison of the gastroprotective effect of 18 new amino acid ester amides was carried out at a single oral dose of 25 mg/kg. Several compounds presented a strong gastroprotective effect, reducing gastric lesions in the 70.9-87.8% range. The diprolyl derivative of junicedric acid, the most active product of this study (87.8% lesion reduction at 25 mg/kg) presented a cytotoxicity value comparable with that of the reference compound lansoprazole. The structure-activity relationships are discussed.

Adipose tissue has acquired considerable importance due to its role in maintaining body homeostasis. Beyond storing energy, adipose tissue is essential in numerous processes of energy metabolism, food intake, endocrine and immunological functions as well as neromodulatory functions by secreting hormones that participate in the regulation of homeostasis and being responsive to soluble proteins secreted by other tissues. An imbalance of these functions will generate structural and functional changes in the adipose tissue, favouring the secretion of deleterious adipocytokines that benefit a pro-inflammatory state, allowing the development of metabolic and cardiovascular diseases. Obesity is a disease that has increased rapidly in recent decades and is caused by environmental, hormonal, and genetic factors, which probably work in combination. Environmental factors that contribute to the increase in obesity include decreased physical activity, associated with increased screen time, increased accessibility and consumption of foods rich in fats and sugars. Weight loss should be recommended for all obese patients and overweight patients with comorbidities. For many patients who need to lose weight for medical reasons, the initial goal is to lose 5-10% of their body weight in the first 6 months. A common theme worldwide has been the development of professional guidelines for the control and treatment of obesity and in Chile, the Chilean Society of Metabolic and Bariatric Surgery led the process of adopting the adult obesity clinical practice guideline, which establishes changes in the approach to managing obesity as a chronic disease, with an emphasis on multifactorial lifestyle interventions that include dietary changes, increased physical activity, and behavioural modifications. Pharmacotherapy, medical devices, and bariatric surgery are other options for patients who need additional interventions, so the objective of this review is to know the pathophysiological mechanisms of obesity from its origin to the current treatments available for treatment.

Cancer is the second cause of death in the world after cardiovascular diseases. Cancer cells acquire capacities not present in normal cells, such as self-sufficiency, resistance to antiproliferative stimuli, evasion of apoptosis, unlimited replication, invasiveness and metastasis. Consequently, it is of major interest to explore and develop molecules with anticancer activity directed to specific targets. In this study, we aimed to evaluate two series of polycyclic quinones: aza-angucyclinone and arylaminopyrimido[4,5-c]isoquinoline-7,10-quinones, in their capacity to inhibit human topoisomerase I (TOP1) and to trigger apoptosis through activation of caspase-3. We evaluated the capacity of the two series of polycyclic quinones to inhibit TOP1, using a DNA supercoiled relaxation assay and their capacity to induce apoptosis through the activation of caspase-3 in HL60 cells. Both series of quinones inhibited TOP1 activity over 50%. When we evaluated the pro-apoptotic capacity of both series of quinones, at therapeutically relevant concentrations, the arylaminoquinones ADPA-1CC (methyl 7-(4-methoxyphenyl)amino-1,3-dimethyl-5,8-dioxo-5,8-dihydroisoquinoline-4-carboxylate), P4 (9-phenylamino-3,4-dihydrophenanthridine-1,7,10(2H)-trione) and the aza-angucyclinone OH-6H (8-hydroxy-2,4-dimethyl-2H,4H-benzo[g]pyrimido[4,5-c]isoquinoline-1,3,7,12-tetraone) increased the caspase-3 activity by approximately 2-fold over the control. The series of the arylaminoquinones and aza-angucyclinones showed differential antiproliferative capacity. We further identified a group of them that showed antiproliferative capacity possibly through inhibition of TOP1 and by activation of caspase-3. This group of molecules may represent a potential pharmacological tool in the treatment against cancer.

Azorella compacta (A. compacta) is a shrub of the Andean Altiplano of Bolivia, Chile and Peru, consumed by local communities as a traditional medicine for several maladies such as diabetes, hepatic and inflammatory diseases. A. compacta is rich in mulinane- and azorellane-type diterpenoids. For two of these, acute hypoglycemic effects have been described, but the impact of A. compacta diterpenoids on fatty liver disease has not been investigated. Therefore, A. compacta organic fractions were prepared using petroleum ether, dichloromethane and methanol. Their content was characterized by UHPLC/MS, revealing the presence of ten diterpenoids, mainly mulinic acid, azorellanol and mulin-11,13-diene. Next, mice fed with a high-fat diet (HFD), a model of metabolic dysfunction-associated fatty liver disease (MAFLD), received one of the fractions in drinking water for two weeks. After this treatment, hepatic parameters were evaluated. The A. compacta fractions did not reduce hyperglycemia or body weight in the HFD-fed mice but increased the serum levels of hepatic transaminases (AST and ALT), reduced albumin and increased bilirubin, indicating hepatic damage, while histopathological alterations such as steatosis, inflammation and necrosis generated by the HFD were, overall, not ameliorated by the fractions. These results suggest that organic A. compacta extracts may generate hepatic complications in patients with MAFLD.