Dietary Fiber and Dyslipidemia

Fibers are abundantly found in vegetables, fruit, beans, cereals, seeds, and tubers. Beans and seeds, alongside prevailing as both of the fiber sources, are the sources of vegetable protein as well. Whereas tubers are a carbohydrate source, which people deem as a staple food. Fiber intake in diets, particularly soluble fibers, has the ability to produce gel in the intestines, inhibiting glucose and cholesterol absorption. Dietary fibers have the ability to bind bile salts in the digestive tract, and disturbed bile reabsorption will stimulate bile synthesis in the liver. Dyslipidemia has a significant role in systemic responses and inflammation in adipose tissues. Inflammation can increase intestinal permeability and adipose tissues. Dyslipidemic management is carried out by altering lifestyles, intervening in suitable diets to reduce LDL levels, and increasing HDL levels. The degree of compliance with diet interventions is seminal to ensure successful dyslipidemic management.

Healthy Subcutaneous and Omental Adipose Tissue Is Associated with High Expression of Extracellular Matrix Components

Obesity is associated with extensive expansion and remodeling of the adipose tissue architecture, including its microenvironment and extracellular matrix (ECM). Although obesity has been reported to induce adipose tissue fibrosis, the composition of the ECM under healthy physiological conditions has remained underexplored and debated. Here, we used a combination of three established techniques (picrosirius red staining, a colorimetric hydroxyproline assay, and sensitive gene expression measurements) to evaluate the status of the ECM in metabolically healthy lean (MHL) and metabolically unhealthy obese (MUO) subjects. We investigated ECM deposition in the two major human adipose tissues, namely the omental and subcutaneous depots. Biopsies were obtained from the same anatomic region of respective individuals. We found robust ECM deposition in MHL subjects, which correlated with high expression of collagens and enzymes involved in ECM remodeling. In contrast, MUO individuals showed lower expression of ECM components but elevated levels of ECM cross-linking and adhesion proteins, e.g., lysyl oxidase and thrombospondin. Our data suggests that subcutaneous fat is more prone to express proteins involved in ECM remodeling than omental adipose tissues. We conclude that a more dynamic ability to deposit and remodel ECM may be a key signature of healthy adipose tissue, and that subcutaneous fat may adapt more readily to changing metabolic conditions than omental fat.

Lipid profile of Wistar rats fed normolipid diets with different fatty acid profiles / Perfil lipídico de ratos Wistar submetidos a dietas normolipídicas com diferentes perfis de ácidos graxos

The development of cardiovascular diseases is characterized by changes in the blood lipid profile, among other factors, which are closely related to the population's eating habits. Therefore, this study aimed to identify the effects of diets with different lipid sources on the lipid profile of Wistar rats. Forty male and adult rats were used, divided into 5 groups (control - 7% soybean oil, CA - 7% canola oil, CO - 7% coconut oil, SO - 7% sunflower oil and LD - 7% lard) and fed normolipidic diets for 30 days. The variables food consumption, weight gain, weight of organs and adipose tissues, blood glucose, lipid profile and cardiovascular risk indicators in the experimental groups were evaluated in the study. The results showed strong compatibility between the CA and control groups, which did not differ in all variables, however, divergences were identified for the other groups. The LD group consumed 11% more than the control group and together with the CO group, gained the least weight. For the variables weight of organs and adipose tissues, glycemia and cardiovascular risk indicators, no significant differences were observed. Among the lipid profile parameters, the levels of triglycerides, total cholesterol and HDL of animals that consumed sunflower oil and lard were significantly reduced compared to those of animals that consumed soybean oil. For the LDL fraction, all groups were similar to the control group, except for the LD group, which had a 58% lower content. The effects observed in the CO, SO and LD groups seem to result from a deficiency of essential fatty acids, since the respective sources do not meet the requirements of these nutrients.

miR-199a Downregulation as a Driver of the NOX4/HIF-1α/VEGF-A Pathway in Thyroid and Orbital Adipose Tissues from Graves′ Patients

Graves’ disease (GD) is an autoimmune thyroiditis often associated with Graves’ orbitopathy (GO). GD thyroid and GO orbital fat share high oxidative stress (OS) and hypervascularization. We investigated the metabolic pathways leading to OS and angiogenesis, aiming to further decipher the link between local and systemic GD manifestations. Plasma and thyroid samples were obtained from patients operated on for multinodular goiters (controls) or GD. Orbital fats were from GO or control patients. The NADPH-oxidase-4 (NOX4)/HIF-1α/VEGF-A signaling pathway was investigated by Western blotting and immunostaining. miR-199a family expression was evaluated following quantitative real-time PCR and/or in situ hybridization. In GD thyroids and GO orbital fats, NOX4 was upregulated and correlated with HIF-1α stabilization and VEGF-A overexpression. The biotin assay identified NOX4, HIF-1α and VEGF-A as direct targets of miR-199a-5p in cultured thyrocytes. Interestingly, GD thyroids, GD plasmas and GO orbital fats showed a downregulation of miR-199a-3p/-5p. Our results also highlighted an activation of STAT-3 signaling in GD thyroids and GO orbital fats, a transcription factor known to negatively regulate miR-199a expression. We identified NOX4/HIF-1α/VEGF-A as critical actors in GD and GO. STAT-3-dependent regulation of miR-199a is proposed as a common driver leading to these events in GD thyroids and GO orbital fats.

Impaired Proliferation, Apoptosis, and Angiogenesis of Adipose-Derived Stem Cells Isolated from Rats during the Course of Diabetes

Background: To characterize the impaired of proliferation, apoptosis, and angiogenic activity in ASCs isolated at different stages of the disease course from rats with type 1 diabetes mellitus (T1DM) rats induced by streptozotocin (STZ). Methods: Adipose tissues of the epididymis were harvested at 0, 4, 8, 12, and 16 weeks after the induction of T1DM in rats and from normal rats at the same time points and the morphological variations were detected by Oil red O staining. ASCs were collected from adipose tissues. Cell proliferation, apoptosis, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) expression were assessed. Results: With the prolongation of the disease course, the size and the morphology of adipocytes were distorted, and intracellular lipid droplets became smaller. After 4 weeks, the proliferation of ASCs was decreased, while apoptosis in ASCs was increased. Furthermore, as the disease proceeded, proliferation decreased and apoptosis increased. VEGF and bFGF expression in ASCs from diabetic rats was downregulated at 8 weeks. Conclusion: At 4 weeks after T1DM induction, the proliferation of ASCs decreased and apoptosis increased. The expression of angiogenic factors in ASCs declined at 8 weeks after T1DM induction. The changes in the proliferation, apoptosis, and angiogenic activity are related to the prolongation of disease course.

A Transcriptomic and Proteomic Atlas of Obesity and Type 2 Diabetes in Cynomolgus Monkeys

Obesity and type 2 diabetes (T2D) remain major global healthcare challenges and developing therapeutics necessitate using nonhuman primate models. Here, we present transcriptomic and proteomic analyses of all the major organs of cynomolgus monkeys with spontaneous obesity or T2D in comparison to healthy controls. Molecular changes occur predominantly in the adipose tissues of individuals with obesity, while extensive expression perturbations among T2D individuals are observed in many tissues, such as the liver, kidney, brain, and heart. Immune response-related pathways are upregulated in obesity and T2D, whereas metabolism and mitochondrial pathways are downregulated. Incorporating human single-cell RNA sequencing findings corroborates the role of macrophages and monocytes in obesity. Moreover, we highlight some potential therapeutic targets including SLC2A1 and PCSK1 in obesity as well as SLC30A8 and SLC2A2 in T2D. Our findings provide insights into tissue-specific molecular foundations of obesity and T2D and reveal the mechanistic links between these two metabolic disorders.

Possible Benefits of Faecalibacterium prausnitzii for Obesity-Associated Gut Disorders

Metabolic disorders are an increasing concern in the industrialized world. Current research has shown a direct link between the composition of the gut microbiota and the pathogenesis of obesity and diabetes. In only a few weeks, an obesity-inducing diet can lead to increased gut permeability and microbial dysbiosis, which contributes to chronic inflammation in the gut and adipose tissues, and to the development of insulin resistance. In this review, we examine the interplay between gut inflammation, insulin resistance, and the gut microbiota, and discuss how some probiotic species can be used to modulate gut homeostasis. We focus primarily on Faecalibacterium prausnitzii, a highly abundant butyrate-producing bacterium that has been proposed both as a biomarker for the development of different gut pathologies and as a potential treatment due to its production of anti-inflammatory metabolites.