Beneficial effects of losartan or telmisartan on the local hepatic renin-angiotensin system to counter obesity in an experimental model.

Background: Obesity has been associated with hepatic overexpression of the renin-angiotensin system (RAS).

Aim: To evaluate the action of two angiotensin II (ANGII) receptor blockers (losartan or telmisartan) on the modulation of local hepatic RAS and the resulting metabolic effects in a diet-induced obesity murine model.

Methods: Twenty C57BL/6 mice were randomly divided into two nutritional groups for 10 wk: control group (C, = 5, 10% of energy as fat) or high-fat group (HF, = 15, 50% of energy as fat).

The renin-angiotensin system as a target to solve the riddle of endocrine pancreas homeostasis.

Local renin-angiotensin system (RAS) in the pancreas is linked to the modulation of glucose-stimulated insulin secretion (GSIS) in beta cells and insulin sensitivity in target tissues, emerging as a promising tool in the prevention and/or treatment of obesity, diabetes, and systemic arterial hypertension. Insulin resistance alters pancreatic islet cell distribution and morphology and hypertrophied islets exhibit upregulated angiotensin II type 1 receptor, which drives oxidative stress, apoptosis, and fibrosis, configuring beta cell dysfunction and diminishing islet lifespan. Pharmacological modulation of RAS has shown beneficial effects in diet-induced obesity model, mainly related to the translational potential that angiotensin receptor blockers and ECA2/ANG (1-7)/MAS receptor axis modulation have when it comes to islet preservation and type 2 diabetes prevention and/or treatment.

GW0742 (PPAR-beta agonist) attenuates hepatic endoplasmic reticulum stress by improving hepatic energy metabolism in high-fat diet fed mice.

Endoplasmic reticulum (ER) stress and hepatic steatosis are intertwined with insulin resistance. PPARs are at the crossroads of these pathways. This study aimed to investigate the effects of GW0742 (PPAR-beta agonist) on hepatic energy metabolism and ER stress in a murine diet-induced obesity model.

Differential actions of PPAR-α and PPAR-β/δ on beige adipocyte formation: A study in the subcutaneous white adipose tissue of obese male mice.

Background And Aims: Obesity compromises adipocyte physiology. PPARs are essential to adipocyte plasticity, but its isolated role in the browning phenomenon is not clear. This study aimed to examine whether activation of PPAR-α or PPAR-β/δ could induce beige cell depots in the subcutaneous white adipose tissue of diet-induced obese mice.

Anti-obesogenic effects of WY14643 (PPAR-alpha agonist): Hepatic mitochondrial enhancement and suppressed lipogenic pathway in diet-induced obese mice.

Non-alcoholic fatty liver disease (NAFLD) presents with growing prevalence worldwide, though its pharmacological treatment remains to be established. This study aimed to evaluate the effects of a PPAR-alpha agonist on liver tissue structure, ultrastructure, and metabolism, focusing on gene and protein expression of de novo lipogenesis and gluconeogenesis pathways, in diet-induced obese mice. Male C57BL/6 mice (three months old) received a control diet (C, 10% of lipids, n = 10) or a high-fat diet (HFD, 50% of lipids, n = 10) for ten weeks.

AT1 receptor antagonist induces thermogenic beige adipocytes in the inguinal white adipose tissue of obese mice.

Purpose: To evaluate whether losartan is able to induce beige adipocytes formation, focusing on the thermogenic gene expression and adipocyte remodeling in the subcutaneous white adipose tissue of diet-induced obese mice.

Methods: Male C57BL/6 mice received a control diet (10% energy as lipids) or a high-fat diet (50% energy as lipids) for 10 weeks, followed by a 5-week treatment with losartan: control group, control-losartan group (10 mg/Kg/day), high-fat group and high-fat-losartan group (10 mg/Kg/day). Biochemical, morphometrical, stereological and molecular approaches were used to evaluate the outcomes.

Differential effects of angiotensin receptor blockers on pancreatic islet remodelling and glucose homeostasis in diet-induced obese mice.

Obesity leads to adverse endocrine pancreas remodelling, reduced islet lifespan and early type 2 diabetes onset. AT1R blockade shows beneficial pleiotropic effects. This study sought to compare the effects of losartan and telmisartan on pancreatic islets remodelling and glucose homeostasis in diet-induced obese mice.

Pregestational maternal obesity impairs endocrine pancreas in male F1 and F2 progeny.

Objective: The aim of this study was to evaluate the effects of maternal obesity on pancreas structure and carbohydrate metabolism in early adult life, focusing on the F1 and F2 generations after F0 maternal pregestational, gestation, and lactation high-fat diet (HF).

Methods: C57 BL/6 female mice (F0) were fed standard chow (SC) or an HF diet for 8 wk before mating and during the gestation and lactation periods to provide the F1 generation (F1-SC and F1-HF). At 3 mo old, F1 females were mated to produce the F2 generation (F2-SC and F2-HF).

Enhanced pan-peroxisome proliferator-activated receptor gene and protein expression in adipose tissue of diet-induced obese mice treated with telmisartan.

Telmisartan has previously been used to target obesity, showing peroxisome proliferator-activated receptor (PPAR) β/δ-related effects in white adipose tissue (WAT). We sought to evaluate whether telmisartan enhances gene and protein expression of all PPAR isoforms in WAT and brown adipose tissue (BAT), as well as their downstream effects upon insulin resistance, adipokine profile and adaptive thermogenesis. Male C57BL/6 mice were fed standard chow (SC; 10% lipids) or high-fat diet (HF; 50% lipids) for 10 weeks.