Revised Protein Sparing Diet in Obesity and Type 2 Diabetes Mellitus.

Effective nutrition therapy is a pressing issue in obesity and type 2 diabetes mellitus (T2DM) management. As such, this research aimed to determine the performance of a revised dietary strategy built on the protein-sparing diet in obesity and type 2 diabetes mellitus with regard to obtaining a rapid and stable improvement in glucometabolic control, body weight, body composition, and energy metabolism when applying the strategy in just twenty-one days. The revised protein-sparing diet differs from the traditional protein-sparing modified fast (PSMF) because it does not include foods. The daily calorie intake of this diet is exclusively derived from Isolate whey protein in addition to a formulation of Isolate whey protein enriched with essential amino acids in free form, with the addition of lipids such as extra virgin olive oil and coconut oil as a source of medium chain fatty acids, where the latter is taken for only the first four days of the diet, together with the use, for the same duration, of extended-release metformin, as the only antihyperglycemic allowed. Anthropometric measurements, bioimpedance analysis, indirect calorimetry, and blood chemistry assessments were conducted at the beginning of the study, time 0 (T0), and at the end, time 1 (T1), i.e., on the 21st day. The main outcomes of the revised protein-sparing diet after only twenty-one days were a reduction in body weight with the predominant loss of visceral atherogenic abdominal fat and, therefore, a possible contextual reduction in ectopic fat deposits together with a simultaneous reduction in insulin resistance and normalization of insulin levels, maintenance of free fat mass and basal metabolism, restoration of metabolic flexibility, and improvement of the glucometabolic and lipidic parameters. These results demonstrate the promising potential of the revised protein-sparing diet as an "etiologic tool" in the integrated nutritional treatment of metabolic diseases such as obesity and type 2 diabetes mellitus.

Pharmacological Anti-Remodelling Effects of Disease-Modifying Drugs in Heart Failure with Reduced Ejection Fraction.

Cardiac remodelling is an adverse phenomenon linked to heart failure progression and an important contributor to heart failure severity. Cardiac remodelling could represent the real therapeutic goal in the treatment of patients with heart failure with reduced ejection fraction, being potentially reversed through different pharmacotherapies. Currently, there are well-established drugs such as angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and ß-blockers with anti-remodelling effects; recently, angiotensin receptor neprilysin inhibitor effects on inhibiting cardiac remodelling (improving N-terminal pro-B-type natriuretic peptide levels, echocardiographic parameters of reverse cardiac remodelling and right ventricular function in patients with heart failure with reduced ejection fraction) were demonstrated. More recently, hemodynamic consequences of gliflozins, reduced cardiac hydrostatic pressure as a possible cause of ventricular remodelling and hypertrophy were proposed to explain potential anti-remodelling effects of gliflozins. Gliflozins exert their cardioprotective effects by attenuating myofibroblast activity and collagen-mediated remodelling. Another postulated mechanism is represented by the reduction in sympathetic activity, through the reduction in renal afferent nervous activity and the suppression of central reflex mechanisms. Benefits of gliflozins on left ventricular hypertrophy, dilation, and systolic and diastolic function were also described. In this review, we aimed to provide a wide overview on cardiac remodelling with a particular focus on possible anti-remodelling effects of angiotensin receptor neprilysin inhibitors and gliflozins.

Impact of senescence on the transdifferentiation process of human hepatic progenitor-like cells.

BACKGROUND: Senescence is characterized by a decline in hepatocyte function, with impairment of metabolism and regenerative capacity. Several models that duplicate liver functions in vitro are essential tools for studying drug metabolism, liver diseases, and organ regeneration. The human HepaRG cell line represents an effective model for the study of liver metabolism and hepatic progenitors. However, the impact of senescence on HepaRG cells is not yet known. AIM: To characterize the effects of senescence on the transdifferentiation capacity and mitochondrial metabolism of human HepaRG cells. METHODS: We compared the transdifferentiation capacity of cells over 10 (passage 10 [P10]) vs P20. Aging was evaluated by senescence-associated (SA) beta-galactosidase activity and the comet assay. HepaRG transdifferentiation was analyzed by confocal microscopy and flow cytometry (expression of cluster of differentiation 49a [CD49a], CD49f, CD184, epithelial cell adhesion molecule [EpCAM], and cytokeratin 19 [CK19]), quantitative PCR analysis (expression of albumin, cytochrome P450 3A4 [CYP3A4], γ-glutamyl transpeptidase [γ-GT], and carcinoembryonic antigen [CEA]), and functional analyses (albumin secretion, CYP3A4, and γ-GT). Mitochondrial respiration and the ATP and nicotinamide adenine dinucleotide (NAD+)/NAD with hydrogen (NADH) content were also measured. RESULTS: SA ß-galactosidase staining was higher in P20 than P10 HepaRG cells; in parallel, the comet assay showed consistent DNA damage in P20 HepaRG cells. With respect to P10, P20 HepaRG cells exhibited a reduction of CD49a, CD49f, CD184, EpCAM, and CK19 after the induction of transdifferentiation. Furthermore, lower gene expression of albumin, CYP3A4, and γ-GT, as well as reduced albumin secretion capacity, CYP3A4, and γ-GT activity were reported in transdifferentiated P20 compared to P10 cells. By contrast, the gene expression level of CEA was not reduced by transdifferentiation in P20 cells. Of note, both cellular and mitochondrial oxygen consumption was lower in P20 than in P10 transdifferentiated cells. Finally, both ATP and NAD+/NADH were depleted in P20 cells with respect to P10 cells. CONCLUSION: SA mitochondrial dysfunction may limit the transdifferentiation potential of HepaRG cells, with consequent impairment of metabolic and regenerative properties, which may alter applications in basic studies.