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1.
Proc Natl Acad Sci U S A ; 121(26): e2317945121, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38889154

RESUMEN

Chaperone-mediated autophagy (CMA) is part of the mammalian cellular proteostasis network that ensures protein quality control, maintenance of proteome homeostasis, and proteome changes required for the adaptation to stress. Loss of proteostasis is one of the hallmarks of aging. CMA decreases with age in multiple rodent tissues and human cell types. A decrease in lysosomal levels of the lysosome-associated membrane protein type 2A (LAMP2A), the CMA receptor, has been identified as a main reason for declined CMA in aging. Here, we report constitutive activation of CMA with calorie restriction (CR), an intervention that extends healthspan, in old rodent livers and in an in vitro model of CR with cultured fibroblasts. We found that CR-mediated upregulation of CMA is due to improved stability of LAMP2A at the lysosome membrane. We also explore the translational value of our observations using calorie-restriction mimetics (CRMs), pharmacologically active substances that reproduce the biochemical and functional effects of CR. We show that acute treatment of old mice with CRMs also robustly activates CMA in several tissues and that this activation is required for the higher resistance to lipid dietary challenges conferred by treatment with CRMs. We conclude that part of the beneficial effects associated with CR/CRMs could be a consequence of the constitutive activation of CMA mediated by these interventions.


Asunto(s)
Restricción Calórica , Autofagia Mediada por Chaperones , Proteína 2 de la Membrana Asociada a los Lisosomas , Lisosomas , Animales , Ratones , Proteína 2 de la Membrana Asociada a los Lisosomas/metabolismo , Proteína 2 de la Membrana Asociada a los Lisosomas/genética , Lisosomas/metabolismo , Humanos , Envejecimiento/metabolismo , Fibroblastos/metabolismo , Proteostasis , Hígado/metabolismo , Ratones Endogámicos C57BL , Masculino , Autofagia
2.
Int J Mol Sci ; 24(6)2023 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-36982444

RESUMEN

The metabolic syndrome (MS) is a cluster of risk factors, such as central obesity, hyperglycemia, dyslipidemia, and arterial hypertension, which increase the probability of causing premature mortality. The consumption of high-fat diets (HFD), normally referred to high-saturated fat diets, is a major driver of the rising incidence of MS. In fact, the altered interplay between HFD, microbiome, and the intestinal barrier is being considered as a possible origin of MS. Consumption of proanthocyanidins (PAs) has a beneficial effect against the metabolic disturbances in MS. However, there are no conclusive results in the literature about the efficacy of PAs in improving MS. This review allows a comprehensive validation of the diverse effects of the PAs on the intestinal dysfunction in HFD-induced MS, differentiating between preventive and therapeutic actions. Special emphasis is placed on the impact of PAs on the gut microbiota, providing a system to facilitate comparison between the studies. PAs can modulate the microbiome toward a healthy profile and strength barrier integrity. Nevertheless, to date, published clinical trials to verify preclinical findings are scarce. Finally, the preventive consumption of PAs in MS-associated dysbiosis and intestinal dysfunction induced by HFD seems more successful than the treatment strategy.


Asunto(s)
Microbioma Gastrointestinal , Síndrome Metabólico , Proantocianidinas , Humanos , Animales , Ratones , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/etiología , Síndrome Metabólico/prevención & control , Proantocianidinas/farmacología , Proantocianidinas/uso terapéutico , Obesidad/metabolismo , Intestinos , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos C57BL , Disbiosis/complicaciones
3.
Int J Mol Sci ; 22(8)2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33917044

RESUMEN

Type-2 diabetes mellitus (T2DM) is a major systemic disease which involves impaired pancreatic function and currently affects half a billion people worldwide. Diet is considered the cornerstone to reduce incidence and prevalence of this disease. Algae contains fiber, polyphenols, ω-3 PUFAs, and bioactive molecules with potential antidiabetic activity. This review delves into the applications of algae and their components in T2DM, as well as to ascertain the mechanism involved (e.g., glucose absorption, lipids metabolism, antioxidant properties, etc.). PubMed, and Google Scholar databases were used. Papers in which whole alga, algal extracts, or their isolated compounds were studied in in vitro conditions, T2DM experimental models, and humans were selected and discussed. This review also focuses on meat matrices or protein concentrate-based products in which different types of alga were included, aimed to modulate carbohydrate digestion and absorption, blood glucose, gastrointestinal neurohormones secretion, glycosylation products, and insulin resistance. As microbiota dysbiosis in T2DM and metabolic alterations in different organs are related, the review also delves on the effects of several bioactive algal compounds on the colon/microbiota-liver-pancreas-brain axis. As the responses to therapeutic diets vary dramatically among individuals due to genetic components, it seems a priority to identify major gene polymorphisms affecting potential positive effects of algal compounds on T2DM treatment.


Asunto(s)
Productos Biológicos/química , Productos Biológicos/farmacología , Ingredientes Alimentarios/análisis , Alimentos Funcionales/análisis , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Microalgas/química , Animales , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Productos Biológicos/uso terapéutico , Biomarcadores , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/metabolismo , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Disbiosis , Metabolismo Energético/efectos de los fármacos , Predisposición Genética a la Enfermedad , Humanos , Hipoglucemiantes/uso terapéutico , Microalgas/clasificación , Microbiota
4.
J Nutr ; 147(6): 1104-1112, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28446627

RESUMEN

Background: Lipoapoptosis has been identified as a key event in the progression of nonalcoholic fatty liver disease (NAFLD), and hence, antiapoptotic agents have been recommended as a possible effective treatment for nonalcoholic steatohepatitis (NASH). Silicon, included in meat as a functional ingredient, improves lipoprotein profiles and liver antioxidant defenses in aged rats fed a high-saturated fat, high-cholesterol diet (HSHCD). However, to our knowledge, the antiapoptotic effect of this potential functional meat on the liver has never been tested.Objective: This study was designed to evaluate the effect of silicon on NASH development and the potential antiapoptotic properties of silicon in aged rats.Methods: One-year-old male Wistar rats weighing ∼500 g were fed 3 experimental diets containing restructured pork (RP) for 8 wk: 1) a high-saturated fat diet, as an NAFLD control, with 16.9% total fat, 0.14 g cholesterol/kg diet, and 46.8 mg SiO2/kg (control); 2) the HSHCD as a model of NASH, with 16.6% total fat, 16.3 g cholesterol/kg diet, and 46.8 mg SiO2/kg [high-cholesterol diet (Chol-C)]; and 3) the HSHCD with silicon-supplemented RP with amounts of fat and cholesterol identical to those in the Chol-C diet, but with 750 mg SiO2/kg (Chol-Si). Detailed histopathological assessments were performed, and the NAFLD activity score (NAS) was calculated. Liver apoptosis and damage markers were evaluated by Western blotting and immunohistochemical staining.Results: Chol-C rats had a higher mean NAS (7.4) than did control rats (1.9; P < 0.001). The score in Chol-Si rats (5.4) was intermediate and different from that in both other groups (P < 0.05). Several liver apoptosis markers-including hepatocyte terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate (dUTP) nick end labeling, cytosolic cytochrome c, apoptosis-inducing factor, caspases 9 and 3, and the mitochondrial Bcl-2-associated X protein (BAX)-to-B-cell lymphoma 2 (BCL2) ratio-were 9-45% lower in Chol-Si than in Chol-C rats (P < 0.05) and did not differ from values in the control group.Conclusions: Supplemental silicon substantially affects NASH development in aged male Wistar rats fed an HSHCD by partially blocking apoptosis. These results suggest that silicon-enriched RP could be used as an effective nutritional strategy in preventing NASH.


Asunto(s)
Apoptosis/efectos de los fármacos , Colesterol en la Dieta/administración & dosificación , Dieta Alta en Grasa , Hígado/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Carne Roja , Silicio/uso terapéutico , Animales , Biomarcadores/metabolismo , Colesterol en la Dieta/metabolismo , Hígado/metabolismo , Hígado/patología , Masculino , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Ratas Wistar , Silicio/farmacología , Dióxido de Silicio/farmacología , Dióxido de Silicio/uso terapéutico , Porcinos , Oligoelementos/farmacología , Oligoelementos/uso terapéutico
5.
Food Funct ; 15(3): 1513-1526, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38229530

RESUMEN

The impact of silicon as a functional ingredient in restructured meat (RM) on lipoprotein composition, metabolism, and oxidation on type 2 diabetes mellitus (T2DM) markers has never been studied. This study aims to evaluate the effect of silicon-enriched-meat consumption on lipidaemia, lipoprotein profile and metabolism, plasma arylesterase, and TBARS and their relationships with glycaemia, insulinaemia, and insulin-signaling markers in late-stage-T2DM rats fed a high-saturated-fat-high-cholesterol (HSFHC) diet. Saturated-fat diets with or without added cholesterol were formulated by mixing a 70% purified diet with 30% freeze-dried RM with or without added silicon. Three groups of seven Wistar rats each were tested. The ED group received the control RM in the framework of a high-saturated-fat diet as early-stage T2DM control. The other two groups received streptozotocin-nicotinamide administration together with the HSFHC diet containing the control RM (LD) or silicon-enriched RM (LD-Si). Scores were created to define the diabetic trend and dyslipidaemia. The ED rats showed hyperglycaemia, hyperinsulinaemia, hypertriglyceridaemia, and triglyceride-rich-VLDLs, suggesting they were in early-stage T2DM. LD rats presented hyperglycaemia, hypoinsulinaemia, and reduced HOMA-beta and insulin signaling markers typical of late-stage T2DM along with hypercholesterolaemia and high amounts of beta-VLDL, IDL, and LDL particles and low arylesterase activity. All these markers were significantly (p < 0.05) improved in LD-Si rats. The diabetic trend and diabetes dyslipidaemia scores showed a high and significant correlation (r = 0.595, p < 0.01). Silicon-enriched-meat consumption counterbalances the negative effects of HSFHC diets, functioning as an active hypolipemic, antioxidant, and antidiabetic dietary ingredient in a T2DM rat model, delaying the onset of late-stage diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hipercolesterolemia , Hiperglucemia , Hiperlipidemias , Ratas , Animales , Dieta Aterogénica , Silicio , Ratas Wistar , Insulina , Carne , Lipoproteínas , Colesterol , Glucemia
6.
Foods ; 13(12)2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38928736

RESUMEN

Silicon included in a restructured meat (RM) matrix (Si-RM) as a functional ingredient has been demonstrated to be a potential bioactive antidiabetic compound. However, the jejunal and hepatic molecular mechanisms by which Si-RM exerts its cholesterol-lowering effects remain unclear. Male Wistar rats fed an RM included in a high-saturated-fat high-cholesterol diet (HSFHCD) combined with a low dose of streptozotocin plus nicotinamide injection were used as late-stage type 2 diabetes mellitus (T2DM) model. Si-RM was included into the HSFHCD as a functional food. An early-stage TD2M group fed a high-saturated-fat diet (HSFD) was taken as reference. Si-RM inhibited the hepatic and intestinal microsomal triglyceride transfer protein (MTP) reducing the apoB-containing lipoprotein assembly and cholesterol absorption. Upregulation of liver X receptor (LXRα/ß) by Si-RM turned in a higher low-density lipoprotein receptor (LDLr) and ATP-binding cassette transporters (ABCG5/8, ABCA1) promoting jejunal cholesterol efflux and transintestinal cholesterol excretion (TICE), and facilitating partially reverse cholesterol transport (RCT). Si-RM decreased the jejunal absorptive area and improved mucosal barrier integrity. Consequently, plasma triglycerides and cholesterol levels decreased, as well as the formation of atherogenic lipoprotein particles. Si-RM mitigated the dyslipidemia associated with late-stage T2DM by Improving cholesterol homeostasis. Silicon could be used as an effective nutritional approach in diabetic dyslipidemia management.

7.
Food Chem ; 450: 139339, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-38657343

RESUMEN

Oxidative stress is prevalent in Type 2 Diabetes Mellitus (T2DM) and has been associated with high meat consumption. Carob Fruit Extract (CFE) contains phenolic compounds, making it a suitable functional ingredient. Current study aims to evaluate the effect of CFE-enriched meat (CFE-meat) consumption on the antioxidant status of proximal and distal colon, and its relationship with fecal phenolic compounds in late-stage T2DM rats. Three groups of eight rats were studied: 1) D, fed control-meat; 2) ED, fed CFE-meat since the beginning of the study; 3) DE, fed CFE-meat after confirming T2DM. CFE-meat consumption reduces colonic oxidative stress mainly in the proximal section and helps to ameliorate glutathione metabolism and antioxidant score. Difference between ED and DE groups were associated with colon homeostasis and T2DM progression suggesting greater fermentation but lower absorption in the DE group. CFE appears as a promising tool to improve the antioxidant status observed in late-stage T2DM.


Asunto(s)
Antioxidantes , Colon , Diabetes Mellitus Tipo 2 , Frutas , Estrés Oxidativo , Fenoles , Extractos Vegetales , Animales , Ratas , Antioxidantes/química , Antioxidantes/metabolismo , Antioxidantes/administración & dosificación , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/farmacología , Frutas/química , Colon/metabolismo , Colon/efectos de los fármacos , Fenoles/química , Fenoles/administración & dosificación , Masculino , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Carne/análisis , Humanos , Ratas Wistar , Gomas de Plantas/química , Gomas de Plantas/administración & dosificación , Galactanos , Mananos
8.
Methods Cell Biol ; 185: 165-195, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38556447

RESUMEN

The mucosal surface of gastrointestinal tract is lined with epithelial cells that establish an effective barrier between the lumen and internal environment through intercellular junctions, preventing the passage of potentially harmful substances. The "intestinal barrier function" consist of a defensive system that prevent the passage of antigens, toxins, and microbial products, while maintains the correct development of the epithelial barrier, the immune system and the acquisition of tolerance toward dietary antigens and intestinal microbiota. Intestinal morphology changes subsequent to nutritional variations, stress, aging or diseases, which can also affect the composition of the microbiota, altering the homeostasis of the intestine. A growing body of evidence suggests that alterations in intestinal barrier function favor the development of exaggerated immune responses, leading to metabolic endotoxemia, which seems to be the origin of many chronic metabolic diseases such as type 2 diabetes mellitus (T2DM). Although the mechanisms are still unknown, the interaction between dietary patterns, gut microbiota, intestinal mucosa, and metabolic inflammation seems to be a key factor for the development of T2DM, among other diseases. This chapter details the different techniques that allow evaluating the morphological and molecular alterations that lead of the intestinal barrier dysfunction in a T2DM experimental model. To induce both diabetic metabolic disturbances and gut barrier disruption, Wistar rats were fed a high-saturated fat and high-cholesterol diet and received a single dose of streptozotocin/nicotinamide. This animal model may contribute to clarify the understanding of the role of intestinal barrier dysfunction on the late-stage T2DM etiology.


Asunto(s)
Diabetes Mellitus Tipo 2 , Ratas , Animales , Diabetes Mellitus Tipo 2/metabolismo , Estreptozocina/metabolismo , Niacinamida/farmacología , Niacinamida/metabolismo , Ratas Wistar , Mucosa Intestinal/metabolismo , Colesterol/metabolismo
9.
Nutr Hosp ; 40(2): 457-464, 2023 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-36927007

RESUMEN

Introduction: Autophagy is a very active process that plays an important role in cell and organ differentiation and remodelling, being a crucial system to guarantee health. This physiological process is activated in starvation and inhibited in the presence of nutrients. This short review comments on the three types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy, as well as different aspects that control autophagy and its relationship with health and degenerative diseases. As autophagy is highly dependent on functional autophagy (ATG) proteins integrating the phagophore, the role of some key ATG genes and epigenes are briefly commented on. The manuscript deepens discussing some central aspects of type-2 diabetes mellitus and their relationship with the cell cleaning process and mitochondria homeostasis maintenance, as well as the mechanisms through which antidiabetic drugs affect autophagy. Well-designed studies are needed to elucidate whether autophagy plays a casual or causal role in T2DM.


Introducción: La autofagia es un proceso muy activo que juega un papel importante en la diferenciación y remodelación de células y órganos, siendo un sistema crucial para garantizar la salud. Este proceso fisiológico se activa en la inanición y se inhibe en presencia de nutrientes. En esta breve revisión se definen los tres tipos de autofagia: macroautofagia, microautofagia y autofagia mediada por chaperonas, y los diferentes aspectos que controlan la autofagia y su relación con la salud y las enfermedades degenerativas. Como la autofagia depende en gran medida de las proteínas de autofagia funcional (ATG) que integran el fagóforo, se comenta brevemente el papel clave de algunos genes y epigenes de las ATG. El manuscrito profundiza discutiendo algunos aspectos centrales de la diabetes mellitus de tipo 2 (DMT2) y su relación con el proceso de limpieza celular y el mantenimiento de la homeostasis mitocondrial, así como los mecanismos a través de cuales los fármacos antidiabéticos afectan a la autofagia. Se necesitan estudios bien diseñados para dilucidar si la autofagia juega un papel de casualidad o causalidad en el desarrollo de la DMT2.


Asunto(s)
Autofagia , Diabetes Mellitus Tipo 2 , Humanos , Autofagia/fisiología , Homeostasis , Mitocondrias
10.
Gels ; 10(1)2023 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-38247756

RESUMEN

Oleogels (OG) and gelled emulsions (GE) were elaborated with a mixture of olive and chia oils (80:20 ratio) without and with the incorporation of the health-related compound curcumin. These were studied to evaluate the influence of the oil structuring system on the lipid hydrolysis and bioaccessibility of three healthy fatty acids (FA) (palmitic, oleic, and α-linolenic acids) and of curcumin, compared to the oil mixture (bulk oil, BO). The oil structuring system influenced the firmness and texture, and the presence of curcumin significantly altered the color parameters. GE showed higher lipid digestibility, with a greater proportion of absorbable fraction (higher content of free FA and monoacylglycerides) than OG, which behaved similarly to BO. The presence of curcumin affected the degree of lipolysis, reducing lipid digestibility in OG and increasing it in GE. As for FA bioaccessibility, although GE presented higher percentages overall, curcumin significantly increased and decreased FA bioaccessibility in OG and GE, respectively. The oil structuring system also influenced the bioaccessibility of curcumin, which was higher in GE. Therefore, when selecting an oil structuring system, their physicochemical properties, the degree of lipid hydrolysis, and the bioaccessibility of both curcumin and the FA studied should all be considered.

11.
Nutr Hosp ; 39(6): 1397-1407, 2022 Dec 20.
Artículo en Español | MEDLINE | ID: mdl-36327123

RESUMEN

Introduction: Previous studies have pointed to a possible relationship between vitamin D deficiency and the severity of the disease promoted by SARS-CoV-2, reducing respiratory and cardiovascular complications caused by a hyperreaction of the immune system known as "cytokine storm". This vitamin exerts multiple functions that depend on the presence and levels of different proteins, such as the vitamin D receptor (VDR) and the vitamin D binding protein (DBP), and the existence of single nucleotide polymorphisms (SNPs) of the genes that encode these proteins. The objective of this review is to assess whether some VDR and GC SNPs are risk factors for the most severe forms of COVID-19 disease and whether they condition the response to vitamin D supplementation. A search was performed in PubMed, Google Scholar and Scielo, finding that genotypes in patients affected by COVID-19, were rarely performed, although some studies find a relationship between different alleles and the severity of the disease. The ApaI polymorphism of the VDR gene stands out, as the minor allele "a" increases the risk of mortality from COVID-19 (OR = 11.828, CI: 2,493-56,104, p = 0.002). Results divergency in the efficacy of vitamin D supplementation suggest the need for a larger number of studies. In conclusion, the study of VDR and GC polymorphisms seems essential to effectively treat vitamin D deficiency and particularly to protect against COVID-19. Well-designed studies are needed to elucidate whether plasma vitamin D levels play a role of casuality or causality.


Introducción: Estudios previos han señalado una posible relación entre la deficiencia de la vitamina D y la severidad de la enfermedad promovida por el SARS-CoV-2, reduciendo las complicaciones respiratorias y cardiovasculares causadas por una respuesta exacerbada del sistema inmune. Esta vitamina ejerce múltiples funciones que dependen de la presencia y niveles de diferentes proteínas, como el receptor de la vitamina D (VDR) y la proteína de unión de la vitamina D (DBP), y de la existencia de polimorfismos de un solo nucleótido (SNP) de los genes que codifican a estas proteínas. El objetivo de esta revisión es evaluar si algunos SNP de VDR y GC son factores de riesgo de las formas más severas de la enfermedad COVID-19 y si condicionan la respuesta a la suplementación con vitamina D. Se realizó una búsqueda en PubMed, Google Scholar y Scielo, encontrándose que son escasos los genotipados en pacientes afectados por COVID-19, aunque algunos trabajos hallan una relación entre diferentes alelos y la severidad de la enfermedad. Destaca el polimorfismo ApaI del gen VDR, el cual alelo menor "a" aumenta el riesgo de mortalidad por COVID-19 (OR = 11,828, CI: 2.493-56.104, p = 0,002). La divergencia de resultados en la eficacia de la suplementación de vitamina D sugiere la necesidad de un mayor número de estudios. En conclusión, el estudio de polimorfismos VDR y GC resulta fundamental para tratar eficazmente la deficiencia de vitamina D y en particular en la protección frente a COVID-19. Se necesitan estudios bien diseñados para dilucidar si los niveles plasmáticos de vitamina D juegan un papel de casualidad o causalidad.


Asunto(s)
COVID-19 , Receptores de Calcitriol , SARS-CoV-2 , Deficiencia de Vitamina D , Proteína de Unión a Vitamina D , Vitamina D , Humanos , COVID-19/complicaciones , COVID-19/mortalidad , Genotipo , Polimorfismo de Nucleótido Simple , Receptores de Calcitriol/genética , Vitamina D/metabolismo , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/genética , Proteína de Unión a Vitamina D/genética
12.
Mol Nutr Food Res ; 66(24): e2200104, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36213967

RESUMEN

SCOPE: Hypercholesterolemia increases the risk of mortality in type 2 diabetes mellitus (T2DM), especially in the late-stage. Consumption of bioactive compounds as functional ingredients would help achieve therapeutic goals for cholesterolemia. Silicon has demonstrated a hypocholesterolemic effect and the ability to reduce fat digestion. However, it is unclear whether silicon exerts such effect in late-stage T2DM (LD) and the intestinal mechanisms involved. METHODS AND RESULTS: Three groups of eight rats were included: early-stage T2DM control (ED), LD, and the LD group treated with silicon (LD-Si) once the rats were diabetic. Morphological alterations of the duodenal mucosa, and levels of markers involve in cholesterol absorption and excretion, beside cholesterolemia, and fecal excretion were assayed. Silicon included as a functional ingredient significantly reduces cholesterolemia in part due to: 1) reducing cholesterol intestinal absorption by decreasing the absorptive area and Acetyl-Coenzyme A acetyltransferase-2 (ACAT2) levels; and 2) increasing cholesterol excretion to the lumen by induction of the liver X receptor (LXR) and consequent increase of adenosine triphosphate-binding cassette transporter (ABCG5/8). CONCLUSIONS: These results provide insight into the intestinal molecular mechanisms by which silicon reduces cholesterolemia and highlights the efficacy of the consumption of silicon-enriched functional foods in late-stage T2DM.


Asunto(s)
Diabetes Mellitus Tipo 2 , Ratas , Animales , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 5 , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Silicio/farmacología , Lipoproteínas/metabolismo , Transportadoras de Casetes de Unión a ATP/fisiología , Colesterol , Hígado/metabolismo
13.
Sci Adv ; 8(46): eabq2733, 2022 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-36383673

RESUMEN

Adipogenesis is a tightly orchestrated multistep process wherein preadipocytes differentiate into adipocytes. The most studied aspect of adipogenesis is its transcriptional regulation through timely expression and silencing of a vast number of genes. However, whether turnover of key regulatory proteins per se controls adipogenesis remains largely understudied. Chaperone-mediated autophagy (CMA) is a selective form of lysosomal protein degradation that, in response to diverse cues, remodels the proteome for regulatory purposes. We report here the activation of CMA during adipocyte differentiation and show that CMA regulates adipogenesis at different steps through timely degradation of key regulatory signaling proteins and transcription factors that dictate proliferation, energetic adaptation, and signaling changes required for adipogenesis.

14.
Food Res Int ; 141: 110124, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33641991

RESUMEN

Epidemiological and experimental studies have suggested that dietary fiber and proanthocyanidins play an important role on gut microbiota (GM), colonic integrity and body health. Type 2 Diabetes Mellitus (T2DM) is a prevalent disease in which the modifications in the GM and colonic markers stand out. This manuscript hypothesizes the consumption of functional meat enriched in carob fruit extract [CFE; CFE-restructured meat (RM)] ameliorates the dysbiosis and colonic barrier integrity loss in a late-stage T2DM rat model induced by the conjoint action of a high-saturated-fat/high-cholesterol diet (Chol-diet) and a low dose of streptozotocin (STZ) plus a nicotinamide (NAD) injection. Three groups of eight rats were used: (1) D group, a T2DM control group, fed the Chol-diet; (2) ED group, a T2DM preventive strategy group fed the CFE-Chol-diet since the beginning of the study; and (3) DE group, a T2DM curative treatment group, fed the CFE-Chol-diet once the diabetic state was confirmed. The study lasted 8 weeks. Amount and variety of GM, feces short-chain-fatty acids (SCFAs), colonic morphology [crypt depth and density, goblet cells, proliferating cell nuclear antigen (PCNA) and transferase dUTP nick end labelling (TUNEL) indexes] and tight junctions were evaluated. A global colonic index combining 17 markers (GCindex) was calculated. ED rats displayed higher levels of GM richness, SCFAs production, crypt depth, and goblet cells than the D group. DE group showed lower Enterobacteriaceae abundance and greater TUNEL index and occludin expression in the distal colon than D counterpart. GCindex differentiated the colonic health status of the experimental groups in the order (ED > DE > D; P < 0.001) as a 17-51 range-quotation, ED, DE, and D groups displayed the values 43, 32.5, and 27, respectively. Thus, CFE-RM used as a T2DM preventive therapy could induce higher GM richness, more adequate SCFAs production, and better colonic barrier integrity. Furthermore, CFE-RM used with curative purposes induced more modest changes and mainly at the distal colonic mucosa. Further studies are needed to confirm this study's results, to ascertain the benefits of consuming proanthocyanidins-rich fiber during different T2DM stages.


Asunto(s)
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Animales , Colon , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/prevención & control , Frutas , Galactanos , Mananos , Carne , Gomas de Plantas , Ratas
15.
Adv Nutr ; 12(4): 1514-1539, 2021 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-33578416

RESUMEN

High meat consumption has been associated with increased oxidative stress mainly due to the generation of oxidized compounds in the body, such as malondialdehyde, 4-hydroxy-nonenal, oxysterols, or protein carbonyls, which can induce oxidative damage. Meat products are excellent matrices for introducing different bioactive compounds, to obtain functional meat products aimed at minimizing the pro-oxidant effects associated with high meat consumption. Therefore, this review aims to summarize the concept and preparation of healthy and functional meat, which could benefit antioxidant status. Likewise, the key strategies regarding meat production and storage as well as ingredients used (e.g., minerals, polyphenols, fatty acids, walnuts) for developing these functional meats are detailed. Although most effort has been made to reduce the oxidation status of meat, newly emerging approaches also aim to improve the oxidation status of consumers of meat products. Thus, we will delve into the relation between functional meats and their health effects on consumers. In this review, animal trials and intervention studies are discussed, ascertaining the extent of functional meat products' properties (e.g., neutralizing reactive oxygen species formation and increasing the antioxidant response). The effects of functional meat products in the frame of diet-gene interactions are analyzed to 1) discover target subjects that would benefit from their consumption, and 2) understand the molecular mechanisms that ensure precision in the prevention and treatment of diseases, where high oxidative stress takes place. Long-term intervention-controlled studies, testing different types and amounts of functional meat, are also necessary to ascertain their positive impact on degenerative diseases.


Asunto(s)
Productos de la Carne , Animales , Antioxidantes/farmacología , Humanos , Malondialdehído , Carne/análisis , Estrés Oxidativo
16.
Antioxidants (Basel) ; 9(7)2020 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-32698505

RESUMEN

High meat and meat-products consumption has been related to degenerative diseases. In addition to their saturated fatty acids and cholesterol contents, oxidation products generated during their production, storage, digestion, and metabolization have been largely implicated. This review begins by summarizing the concept of meat and meat-products by the main international regulatory agencies while highlighting the nutritional importance of their consumption. The review also dials in the controversy of white/red meat classification and insists in the need of more accurate classification based on adequate scores. Since one of the negative arguments that meat receives comes from the association of its consumption with the increase in oxidative stress, main oxidation compounds (malondialdehyde, thermaloxidized compounds, 4-hydroxy-nonenal, oxysterols, or protein carbonyls) generated during its production, storage, and metabolization, are included as a central aspect of the work. The review includes future remarks addressed to study the effects meat consumption in the frame of diet-gene interactions, stressing the importance of knowing the genetic variables that make individuals more susceptible to a possible oxidative stress imbalance or antioxidant protection. The importance of consumed meat/meat-products in the frame of a personalized nutrition reach in plant-food is finally highlighted considering the importance of iron and plant biophenols on the microbiota abundance and plurality, which in turn affect several aspects of our physiology and metabolism.

17.
Foods ; 9(11)2020 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-33147776

RESUMEN

This paper examines the effect of the type of the emulsifying protein (EP) (sodium caseinate (SC) and whey protein isolate (WPI)) on both oil-in-water liquid-like emulsions (Es) and the corresponding cold gelled emulsions (GEs), and also the effect of addition of carob extract rich in condensed tannins (T). The systems, intended as functional food ingredients, were studied in various different respects, including rheological behaviour, in vitro gastrointestinal digestion with determination of the release of non-extractable proanthocyanidins (NEPA) from T, antioxidant activity and lipolysis. EP significantly affects the rheological behaviour of both Es and GEs. T incorporation produced a structural reinforcement of GEs, especially in the case of SC. The digests from Es displayed a higher antioxidant activity than those from GEs. T lipase inhibition was observed only in the formulations with WPI. Our results highlight the importance, in the design of functional foods, of analyzing different variables when incorporating a bioactive compound into a food or emulsion in order to select the better combination for the desired objective, owing to the complex interplay of the various components.

18.
J Nutr Biochem ; 84: 108461, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32739787

RESUMEN

The inclusion of functional bioactive compounds of dietary fiber in meat products has been demonstrated to exert a significant impact on human health. Carob fruit extract (CFE) is a dietary fiber rich in proanthocyanidins with known antioxidant, hypolipidemic and hypoglycemic effects. Consumption of CFE-enriched meat (CFE-RM) may provide interesting benefits in late-stage type 2 diabetes mellitus (T2DM). To explore the antidiabetic mechanisms of CFE-RM, we used a model of late-stage T2DM in Wistar rats fed a high-saturated-fat/high-cholesterol diet (Chol-diet) and injected streptozotocin plus nicotinamide (D group). The effects of CFE-RM were tested by incorporating it into the diet as preventive strategy (ED group) or curative treatment (DE group). CFE-RM had a positive effect on glycemia, enhancing hepatic insulin sensitivity and improving pancreatic ß-cell regeneration in both ED and DE groups. Western blotting and immunohistochemistry suggested that CFE-RM increased levels of insulin receptor ß and phosphatidylinositol-3-kinase, as well as the downstream target phospho-Akt (at Ser473). CFE-RM also up-regulated glucose transporter 2, which improves the insulin-mediated glucose uptake by the liver, and promoted phosphorylation of glycogen synthesis kinase-3ßprotein (at ser9), consequently increasing the hepatic glycogen content. In addition, CFE-RM decreased fatty liver by suppressing de novo lipogenesis activation due to down-regulation of liver X receptor-α/ß, sterol regulatory element binding protein-1c and carbohydrate-response element-binding protein transcription factors. Our findings suggest that the consumption of CFE-RM included in the diet as a functional food should be considered as a suitable nutritional strategy to prevent or manage late-stage T2DM.


Asunto(s)
Diabetes Mellitus Tipo 2/terapia , Fibras de la Dieta , Alimentos Funcionales , Insulina/metabolismo , Lipogénesis , Carne , Animales , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Fibras de la Dieta/análisis , Fibras de la Dieta/metabolismo , Fibras de la Dieta/uso terapéutico , Hígado/metabolismo , Hígado/patología , Masculino , Carne/análisis , Ratas Wistar
19.
Nutrients ; 11(7)2019 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-31295866

RESUMEN

The prevalence of degenerative diseases has risen in western countries. Growing evidence suggests that demenia and other cognition affectations are associated with ambient factors including specific nutrients, food ingredients or specific dietary patterns. Mediterranean diet adherence has been associated with various health benefits and decreased risk of many diseases, including neurodegenerative disorders. Beer, as part of this protective diet, contains compounds such as silicon and hops that could play a major role in preventing brain disorders. In this review, different topics regarding Mediterranean diet, beer and the consumption of their main compounds and their relation to neurological health have been addressed. Taking into account published results from our group and other studies, the hypothesis linking aluminum intoxication with dementia and/or Alzheimer's disease and the potential role of regular beer has also been considered. Beer, in spite of its alcohol content, may have some health benefits; nonetheless, its consumption is not adequate for all subjects. Thus, this review analyzed some promising results of non-alcoholic beer on several mechanisms engaged in neurodegeneration such as inflammation, oxidation, and cholinesterase activity, and their contribution to the behavioral modifications induced by aluminum intoxication. The review ends by giving conclusions and suggesting future topics of research related to moderate beer consumption and/or the consumption of its major compounds as a potential instrument for protecting against neurodegenerative disease progression and the need to develop nutrigenetic and nutrigenomic studies in aged people and animal models.


Asunto(s)
Enfermedad de Alzheimer , Cerveza , Dieta Mediterránea , Neuroprotección , Aluminio , Humanos , Valor Nutritivo , Silicio
20.
Nutrients ; 11(2)2019 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-30717491

RESUMEN

Carob fruit extract (CFE) has shown remarkable in vitro antioxidant properties and reduces postprandial hyperglycemia and hyperlipidemia in healthy animals. Development of functional meat products that contain bioactive components are presented as a great nutritional strategy. Until now, the effect of the consumption of restructured meat enriched with CFE in a murine model of diabetes has not been investigated. The objective of this study was to evaluate the effect on glycemia, lipemia, lipoprotein profile, Ldlr, arylesterase (AE), and very low-density lipoproteins (VLDL) and liver oxidation in streptozotocin-nicotinamide (STZ-NAD) growing Wistar diabetic rats fed restructured meat in the frame of a high cholesterol/high saturated-fat diet. In the present study, three groups (D, ED and DE) were fed cholesterol-enriched (1.4% cholesterol and 0.2% cholic acid) and high saturated-fat diets (50% of total energy from fats and 20.4% from saturated fatty acids). Rats were subjected to a STZ-NAD administration at the 3rd week. Group D did not receive CFE, while ED and DE rat groups received CFE before and after the diabetic induction, respectively. After eight weeks, D rats showed hyperglycemia and hypercholesterolemia, an increased amount cholesterol-enriched VLDL (ß-VLDL), IDL and LDL particles and triglyceride-enriched HDL. ED and DE partially blocked the hypercholesterolemic induction with respect to D group (p < 0.001) and improved glycemia, cholesterol levels, lipoprotein profile, Ldlr, plasma AE activity and liver oxidation (p < 0.001). Fecal fat, moisture and excretion were higher while dietary digestibility was lower in ED and DE vs. D counterparts (p < 0.001). In conclusion, CFE-enriched meat shows, for the first time, hypoglycemic and hypolipidemic effects in STZ-NAD animals fed high cholesterol/high saturated-fat diets. Likewise, it manages to reverse possible diabetes lipoprotein alterations if CFE-enriched meat is consumed before pathology development or improves said modifications if Type 2 Diabetes Mellitus is already established.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Dieta Aterogénica/efectos adversos , Fabaceae , Lipoproteínas VLDL/sangre , Carne , Extractos Vegetales/uso terapéutico , Receptores de LDL/sangre , Animales , Glucemia/metabolismo , Hidrolasas de Éster Carboxílico/sangre , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Grasas de la Dieta/efectos adversos , Digestión , Heces , Manipulación de Alimentos , Frutas , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Hipolipemiantes/farmacología , Hipolipemiantes/uso terapéutico , Lipoproteínas/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Ratas Wistar , Triglicéridos/sangre
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