The peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that promote ligand-dependent transcription of target genes that regulate energy production, lipid metabolism, and inflammation. The PPAR superfamily comprises three subtypes, PPARα, PPARγ, and PPARβ/δ, with differential tissue distributions. In addition to their different roles in the regulation of energy balance and carbohydrate and lipid metabolism, an emerging function of PPARs includes normal homeostasis of intestinal tissue. PPARα activation represses NF-κB signaling, which decreases the inflammatory cytokine production by different cell types, while PPARγ ligands can inhibit activation of macrophages and the production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and Il-1β. In this regard, the anti-inflammatory responses induced by PPAR activation might restore physiopathological imbalances associated with inflammatory bowel diseases (IBD). Thus, PPARs and their ligands have important therapeutic potential. This review briefly discusses the roles of PPARs in the physiopathology and therapies of the most important IBDs, ulcerative colitis (UC), and Crohn's disease (CD), as well some new experimental compounds with PPAR activity as promising drugs for IBD treatment.

Inositols are sugar-like compounds that are widely distributed in nature and are a part of membrane molecules, participating as second messengers in several cell-signaling processes. Isolation and characterization of inositol phosphoglycans containing myo- or d-chiro-inositol have been milestones for understanding the physiological regulation of insulin signaling. Other functions of inositols have been derived from the existence of multiple stereoisomers, which may confer antioxidant properties. In the brain, fluctuation of inositols in extracellular and intracellular compartments regulates neuronal and glial activity. Myo-inositol imbalance is observed in psychiatric diseases and its use shows efficacy for treatment of depression, anxiety, and compulsive disorders. Epi- and scyllo-inositol isomers are capable of stabilizing non-toxic forms of β-amyloid proteins, which are characteristic of Alzheimer’s disease and cognitive dementia in Down’s syndrome, both associated with brain insulin resistance. However, uncertainties of the intrinsic mechanisms of inositols regarding their biology are still unsolved. This work presents a critical review of inositol actions on insulin signaling, oxidative stress, and endothelial dysfunction, and its potential for either preventing or delaying cognitive impairment in aging and neurodegenerative diseases. The biomedical uses of inositols may represent a paradigm in the industrial approach perspective, which has generated growing interest for two decades, accompanied by clinical trials for Alzheimer’s disease.

Increasing evidence links metabolic disorders with neurodegenerative processes including Alzheimer’s disease (AD). Late AD is associated with amyloid (Aβ) plaque accumulation, neuroinflammation, and central insulin resistance. Here, a humanized AD model, the 5xFAD mouse model, was used to further explore food intake, energy expenditure, neuroinflammation, and neuroendocrine signaling in the hypothalamus. Experiments were performed on 6-month-old male and female full transgenic (Tg^5xFAD/5xFAD), heterozygous (Tg^5xFAD/-), and non-transgenic (Non-Tg) littermates. Although histological analysis showed absence of Aβ plaques in the hypothalamus of 5xFAD mice, this brain region displayed increased protein levels of GFAP and IBA1 in both Tg^5xFAD/- and Tg^5xFAD/5xFAD mice and increased expression of IL-1β in Tg^5xFAD/5xFAD mice, suggesting neuroinflammation. This condition was accompanied by decreased body weight, food intake, and energy expenditure in both Tg^5xFAD/- and Tg^5xFAD/5xFAD mice. Negative energy balance was associated with altered circulating levels of insulin, GLP-1, GIP, ghrelin, and resistin; decreased insulin and leptin hypothalamic signaling; dysregulation in main metabolic sensors (phosphorylated IRS1, STAT5, AMPK, mTOR, ERK2); and neuropeptides controlling energy balance (NPY, AgRP, orexin, MCH). These results suggest that glial activation and metabolic dysfunctions in the hypothalamus of a mouse model of AD likely result in negative energy balance, which may contribute to AD pathogenesis development.

The embryonic epicardium generates a population of epicardial‐derived mesenchymal cells (EPDC) whose contribution to the coronary endothelium is minor or, according to some reports, negligible. We have compared four murine cell‐tracing models related to the EPDC in order to elucidate this contribution. Cre recombinase was expressed under control of the promoters of the Wilms' tumor suppressor ( Wt1 ), the cardiac troponin ( cTnT ), and the GATA5 genes, activating expression of the R26R ^EYFP reporter. We have also used the G2 enhancer of the GATA4 gene as a driver due to its activation in the proepicardium. Recombination was found in most of the epicardium/EPDC in all cases. The contribution of these lineages to the cardiac endothelium was analyzed using confocal microscopy and flow cytometry. G2‐GATA4 lineage cells are the most frequent in the endothelium, probably due to the recruitment of circulating endothelial progenitors. The contribution of the WT1 cell lineage increases along gestation due to further endothelial expression of WT1. GATA5 and cTnT lineages represent 4% of the cardiac endothelial cells throughout the gestation, probably standing for the actual EPDC contribution to the coronary endothelium. These results suggest caution when using a sole cell‐tracing model to study the fate of the EPDC.