Epigenetic reprogramming of H3K4me3 in adipose-derived stem cells by HFS diet consumption leads to a disturbed transcriptomic profile in adipocytes.

Adipose tissue metabolism is actively involved in the regulation of energy balance. Adipose-derived stem cells (ASCs) play a critical role in maintaining adipose tissue function through their differentiation into mature adipocytes (Ad). This study aimed to investigate the impact of an obesogenic environment on the epigenetic landscape of ASCs and its impact on adipocyte differentiation and its metabolic consequences. Our results showed that ASCs from rats on a high-fat sucrose (HFS) diet displayed reduced adipogenic capacity, increased fat accumulation, and formed larger adipocytes than the control (C) group. Mitochondrial analysis revealed heightened activity in undifferentiated ASC-HFS but decreased respiratory and glycolytic capacity in mature adipocytes. The HFS diet significantly altered the H3K4me3 profile in ASCs on genes related to adipogenesis, mitochondrial function, inflammation, and immunomodulation. After differentiation, adipocytes retained H3K4me3 alterations, confirming the upregulation of genes associated with inflammatory and immunomodulatory pathways. RNA-seq confirmed the upregulation of genes associated with inflammatory and immunomodulatory pathways in adipocytes. Overall, the HFS diet induced significant epigenetic and transcriptomic changes in ASCs, impairing differentiation and causing dysfunctional adipocyte formation.NEW & NOTEWORTHY Obesity is associated with the development of chronic diseases like metabolic syndrome and type 2 diabetes, and adipose tissue plays a crucial role. In a rat model, our study reveals how an obesogenic environment primes adipocyte precursor cells, leading to epigenetic changes that affect inflammation, adipogenesis, and mitochondrial activity after differentiation. We highlight the importance of histone modifications, especially the trimethylation of histone H3 to lysine 4 (H3K4me3), showing its influence on adipocyte expression profiles.

Effect of the intake of dietary protein on insulin resistance in subjects with obesity: a randomized controlled clinical trial.

PURPOSE: We compared the effect of diets with different amounts and sources of dietary protein on insulin sensitivity (IS) in subjects with obesity and insulin resistance (IR). METHODS: Eighty subjects with obesity (BMI ≥ 30 kg/m2) and IR (Matsuda index < 4.3 and HOMA-IR ≥ 2.5) over 18 years old were randomized to four groups for a one-month period: a normal protein diet (< 20%) with a predominance of animal protein (Animal NP) or vegetable protein (Vegetable NP) and a high-protein diet (25-30%) with a predominance of animal protein (Animal HP) or vegetable protein (Vegetable HP). Baseline and final measurements of body weight, body composition, biochemical parameters, blood pressure (BP), resting energy expenditure and plasma amino acid profiles were performed. RESULTS: Body weight, BMI and waist circumference decreased in all groups. Interestingly, the IS improved more in the Animal HP (Matsuda index; 1.39 vs 2.58, P = 0.003) and in the Vegetable HP groups (Matsuda index; 1.44 vs 3.14, P < 0.0001) after one month. The fat mass, triglyceride levels, C-reactive protein levels and the leptin/adiponectin index decreased; while, the skeletal muscle mass increased in the Animal and Vegetable HP groups. The BP decreased in all groups except the Animal NP group. CONCLUSION: Our study demonstrates that a high-protein hypocaloric diets improves IS by 60-90% after one month in subjects with obesity and IR, regardless of weight loss and the source of protein, either animal or vegetable. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT03627104), August 13, 2018.

Pancreatic insulin secretion in rats fed a soy protein high fat diet depends on the interaction between the amino acid pattern and isoflavones.

Obesity is frequently associated with the consumption of high carbohydrate/fat diets leading to hyperinsulinemia. We have demonstrated that soy protein (SP) reduces hyperinsulinemia, but it is unclear by which mechanism. Thus, the purpose of the present work was to establish whether SP stimulates insulin secretion to a lower extent and/or reduces insulin resistance, and to understand its molecular mechanism of action in pancreatic islets of rats with diet-induced obesity. Long-term consumption of SP in a high fat (HF) diet significantly decreased serum glucose, free fatty acids, leptin, and the insulin:glucagon ratio compared with animals fed a casein HF diet. Hyperglycemic clamps indicated that SP stimulated insulin secretion to a lower extent despite HF consumption. Furthermore, there was lower pancreatic islet area and insulin, SREBP-1, PPARgamma, and GLUT-2 mRNA abundance in comparison with rats fed the casein HF diet. Euglycemic-hyperinsulinemic clamps showed that the SP diet prevented insulin resistance despite consumption of a HF diet. Incubation of pancreatic islets with isoflavones reduced insulin secretion and expression of PPARgamma. Addition of amino acids resembling the plasma concentration of rats fed casein stimulated insulin secretion; a response that was reduced by the presence of isoflavones, whereas the amino acid pattern resembling the plasma concentration of rats fed SP barely stimulated insulin release. Infusion of isoflavones during the hyperglycemic clamps did not stimulate insulin secretion. Therefore, isoflavones as well as the amino acid pattern seen after SP consumption stimulated insulin secretion to a lower extent, decreasing PPARgamma, GLUT-2, and SREBP-1 expression, and ameliorating hyperinsulinemia observed during obesity.

Índice glicémico, índice insulinémico y carga glicémica de bebidas de soya con un contenido bajo y alto en hidratos de carbono / Glycemic, insulinemic index, glycemic load of soy beverage with low and high content of carbohydrates

Consumption of soy has increased in Western countries due to the benefits on health and the attitude of the people to consume natural products as alternative to the use of pharmacological therapies. However, there is no evidence whether the consumption of 25 g of soy protein as recommended by the Food and Drug Administration has some effect on glucose absorption and consequently on insulin secretion. The aim of the present study was to determine glycemic index (GI), insulinemic index (InIn), and glycemic load (GL) of several soy beverages containing low or high concentration of carbohydrates, and compare them with other foods such as peanuts, whole milk, soluble fiber and a mixed meal on GI and InIn. The results showed that soy beverages had low or moderate GI, depending of the presence of other compounds like carbohydrates and fiber. Consumption of soy beverages with low concentration of carbohydrates produced the lowest insulin secretion. Therefore, these products can be recommended in obese and diabetic patients. Finally soy beverages should contain low maltodextrins concentration and be added of soluble fiber.

El consumo de soya se ha incrementado en países occidentales debido a sus beneficios sobre la salud y por la toma de conciencia de la gente a consumir productos naturales como alternativa a los medicamentos. Sin embargo, no se conoce totalmente si el consumo de 25 g de proteína de soya como recomienda la Administración de Alimentos y Medicamentos de Estados Unidos (FDA) tiene algún efecto sobre la absorción de glucosa y su respuesta sobre la secreción de insulina. Por lo que el objetivo del presente trabajo fue determinar el índice glicémico (IG), índice insulinémico (InIn) y la carga glicémica (CG) de diferentes bebidas de soya con un bajo y alto contenido de hidratos de carbono y compararlos con otros alimentos como cacahuates, la leche entera, la fibra soluble y una comida para ver el efecto de los hidratos de carbono, la fibra y la grasa sobre los IG e InIn. Los resultados muestran que las bebidas de soya presentan un IG bajo a moderado dependiendo de la presencia de otros componentes como son los hidratos de carbono y la fibra. La secreción de insulina fue significativamente menor en las bebidas de soya con bajo contenido de hidratos de carbono, por lo que pueden ser recomendadas en pacientes obesos con resistencia a la insulina o en pacientes diabéticos. Se recomienda que estas bebidas tengan bajo contenido en maltodextrinas y de preferencia con la adición de fibra soluble.

[Glycemic, insulinemic index, glycemic load of soy beverage with low and high content of carbohydrates]. / Indice glicémico, índice insulinémico y carga glicémica de bebidas de soya con un contenido bajo y alto en hidratos de carbono.

Consumption of soy has increased in Western countries due to the benefits on health and the attitude of the people to consume natural products as alternative to the use of pharmacological therapies. However, there is no evidence whether the consumption of 25 g of soy protein as recommended by the Food and Drug Administration has some effect on glucose absorption and consequently on insulin secretion. The aim of the present study was to determine glycemic index (GI), insulinemic index (InIn), and glycemic load (GL) of several soy beverages containing low or high concentration of carbohydrates, and compare them with other foods such as peanuts, whole milk, soluble fiber and a mixed meal on GI and InIn. The results showed that soy beverages had low or moderate GI, depending of the presence of other compounds like carbohydrates and fiber. Consumption of soy beverages with low concentration of carbohydrates produced the lowest insulin secretion. Therefore, these products can be recommended in obese and diabetic patients. Finally soy beverages should contain low maltodextrins concentration and be added of soluble fiber.