Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.

Nonalcoholic steatohepatitis (NASH) is recognized by hepatic lipid accumulation, inflammation, and fibrosis. No studies have evaluated the prolonged‐release pirfenidone (PR‐PFD) properties on NASH features. The aim of this study is to evaluate how PR‐PFD performs on metabolic functions, and provide insight on a mouse model of human NASH. Male C57BL/6J mice were fed with either normo diet or high‐fat/carbohydrate diet for 16 weeks and a subgroup also fed with PR‐PFD (300 mg/kg/day). An insulin tolerance test was performed at the end of treatment. Histological analysis, determination of serum hormones, adipocytokines measurement, and evaluation of proteins by western blot was performed. Molecular docking, in silico site‐directed mutagenesis, and in vitro experiments using HepG2 cultured cells were performed to validate PR‐PFD binding to peroxisome proliferator–activated receptor alpha (PPAR‐α), activation of PPAR‐α promoter, and sirtuin 1 (SIRT1) protein expression. Compared with the high‐fat group, the PR‐PFD‐treated mice displayed less weight gain, cholesterol, very low density lipoprotein and triglycerides, and showed a significant reduction of hepatic macrosteatosis, inflammation, hepatocyte ballooning, fibrosis, epididymal fat, and total adiposity. PR‐PFD restored levels of insulin, glucagon, adiponectin, and resistin along with improved insulin resistance. Noteworthy, SIRT1–liver kinase B1–phospho‐5′ adenosine monophosphate–activated protein kinase signaling and the PPAR‐α/carnitine O‐palmitoyltransferase 1/acyl‐CoA oxidase 1 pathway were clearly induced in high fat + PR‐PFD mice. In HepG2 cells incubated with palmitate, PR‐PFD induced activation and nuclear translocation of both PPARα and SIRT1, which correlated with increased SIRT1 phosphorylated in serine 47, suggesting a positive feedback loop between the two proteins. These results were confirmed with both synthetic PPAR‐α and SIRT1 activators and inhibitors. Finally, we found that PR‐PFD is a true agonist/ligand for PPAR‐α. Conclusions: PR‐PFD provided an anti‐steatogenic effect and protection for inflammation and fibrosis.

Eye drug delivery, particularly to the retina, is a technical hurdle that needs to be solved and represents an ongoing current important medical field. Posterior segment eye diseases are a major cause of visual impairment worldwide. Age-related macular degeneration, glaucoma, and diabetic retinopathy are the major causes of blindness. To achieve efficient drug delivery and drug retention time in the posterior segment of the eye, novel delivery systems based on nanoparticles have been developed in the last few years. Nowadays, liposomes represent the most utilized nanoparticles for eye drug delivery and, recently, a broad spectrum of diverse nanoparticles continue to emerge with special characteristics representing ideal candidates for eye drug delivery.

Carbohydrates and lipids are two components of the diet that provide the necessary energy to carry out various physiological processes to help maintain homeostasis in the body. However, when the metabolism of both biomolecules is altered, development of various liver diseases takes place; such as metabolic-associated fatty liver diseases (MAFLD), hepatitis B and C virus infections, alcoholic liver disease (ALD), and in more severe cases, hepatocelular carcinoma (HCC). On the other hand, PPARs are a family of ligand-dependent transcription factors with an important role in the regulation of metabolic processes to hepatic level as well as in other organs. After interaction with specific ligands, PPARs are translocated to the nucleus, undergoing structural changes to regulate gene transcription involved in lipid metabolism, adipogenesis, inflammation and metabolic homeostasis. This review aims to provide updated data about PPARs’ critical role in liver metabolic regulation, and their involvement triggering the genesis of several liver diseases. Information is provided about their molecular characteristics, cell signal pathways, and the main pharmacological therapies that modulate their function, currently engaged in the clinic scenario, or in pharmacological development.

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