Feeding induces cholesterol biosynthesis via the mTORC1–USP20–HMGCR axis

Nature, Год журнала: 2020, Номер 588(7838), С. 479 - 484

Опубликована: Ноя. 11, 2020

Язык: Английский

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PDK4 dictates metabolic resistance to ferroptosis by suppressing pyruvate oxidation and fatty acid synthesis

Cell Reports, Год журнала: 2021, Номер 34(8), С. 108767 - 108767

Опубликована: Фев. 1, 2021

Although induction of ferroptosis, an iron-dependent form non-apoptotic cell death, has emerged as anticancer strategy, the metabolic basis ferroptotic death remains poorly elucidated. Here, we show that glucose determines sensitivity human pancreatic ductal carcinoma cells to ferroptosis induced by pharmacologically inhibiting system xc−. Mechanistically, SLC2A1-mediated uptake promotes glycolysis and, thus, facilitates pyruvate oxidation, fuels tricyclic acid cycle, and stimulates fatty synthesis, which finally lipid peroxidation-dependent death. Screening a small interfering RNA (siRNA) library targeting enzymes leads identification dehydrogenase kinase 4 (PDK4) top gene responsible for resistance. PDK4 inhibits blocking dehydrogenase-dependent oxidation. Inhibiting enhances activity xc− inhibitors in vitro suitable preclinical mouse models (e.g., high-fat diet diabetes model). These findings reveal reprogramming potential target overcoming

Язык: Английский

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Solute carrier transporters: the metabolic gatekeepers of immune cells

Acta Pharmaceutica Sinica B, Год журнала: 2019, Номер 10(1), С. 61 - 78

Опубликована: Дек. 15, 2019

Solute carrier (SLC) transporters meditate many essential physiological functions, including nutrient uptake, ion influx/efflux, and waste disposal. In its protective role against tumors infections, the mammalian immune system coordinates complex signals to support proliferation, differentiation, effector function of individual cell subsets. Recent research in this area has yielded surprising findings on roles solute transporters, which were discovered regulate lymphocyte signaling control their function, fate by modulating diverse metabolic pathways balanced levels different metabolites. review, we present current information mainly glucose amino-acid metal are critically important for mediating homeostasis pathological conditions.

Язык: Английский

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Tricarboxylic Acid (TCA) Cycle Intermediates: Regulators of Immune Responses

Life, Год журнала: 2021, Номер 11(1), С. 69 - 69

Опубликована: Янв. 19, 2021

The tricarboxylic acid cycle (TCA) is a series of chemical reactions used in aerobic organisms to generate energy via the oxidation acetylcoenzyme A (CoA) derived from carbohydrates, fatty acids and proteins. In eukaryotic system, TCA occurs completely mitochondria, while intermediates are retained inside mitochondria due their polarity hydrophilicity. Under cell stress conditions, can become disrupted release contents, which act as danger signals cytosol. Of note, may also leak dysfunctioning regulate cellular processes. Increasing evidence shows that metabolites substantially involved regulation immune responses. this review, we aimed provide comprehensive systematic overview molecular mechanisms each intermediate play key roles regulating immunity discuss its implication for activation suppression.

Язык: Английский

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Insulin resistance and cardiovascular disease

Journal of International Medical Research, Год журнала: 2023, Номер 51(3)

Опубликована: Март 1, 2023

Insulin resistance (IR) and cardiovascular disease (CVD) represent two universal public health hazards, especially in today’s Western societies. A causal-effect relationship has been established that links IR with CVD. The mediating mechanisms are perplexing, under ongoing, rigorous investigation remain to be fully elucidated. is a condition encompassing hyperglycemia compensatory hyperinsulinemia. It occurs when insulin not capable of exerting its maximum effects on target tissues, including skeletal muscles, liver adipose tissue. This alteration signaling pathways results the development cardiometabolic disorders, obesity, dyslipidemia, low-grade inflammation, endothelial dysfunction hypertension, all which predisposing factors for atherosclerosis management can achieved through dietary modifications, inclusion regular exercise routines everyday life, pharmacological agents other interventions tailored each individual patient’s needs. important underline though that, although various antidiabetic drugs may improve available, no medications as yet specifically approved treatment IR. narrative review will focus current scientific clinical evidence pertaining IR, connecting CVD, well plausible strategies holistic, personalized approach management.

Язык: Английский

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TMEM41B acts as an ER scramblase required for lipoprotein biogenesis and lipid homeostasis

Cell Metabolism, Год журнала: 2021, Номер 33(8), С. 1655 - 1670.e8

Опубликована: Май 19, 2021

Язык: Английский

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Incidence and long-term specific mortality trends of metabolic syndrome in the United States

Frontiers in Endocrinology, Год журнала: 2023, Номер 13

Опубликована: Янв. 17, 2023

Purpose Metabolic syndrome (MetS) is extremely prevalent and related to severe diseases death. This study aims investigate the incidence mortality trends among MetS over past few decades. The gender age differences of are also explored. Patients methods Adults with were screened in National Health Nutrition Examination Survey (NHANES) from 1999 2014. data acquired. Then we assessed United States. Results Our included 14171 participants a mean 46.8 ± 19.3 years, whom 7354 (51.9%) women. Among them, 4789 subsequently diagnosed MetS. From 2014, overall trend increased (from 27.6 32.3%; adjusted odds ratios [aOR], 1.71; 95% confidence interval [CI], 1.42-2.05; P -value <0.001, for <0.001). In more detail, rose first but plateaued declined. Obvious downward observed 29.6 2.7% all-cause (aOR, 0.12; 95%CI, 0.07-0.21; <0.001) 4.8 0.8% cardio-cerebrovascular 0.17; 0.05-0.61; =0.007, All-cause decreased yearly, whereas death briefly before declining stabilizing. Similarly, temporal patients different ages genders had same results. Specifically, was higher women than men (adjusted =0.003; OR, 1.14; 1.05-1.24), significantly lower after an average 7.7 years follow-up (all-cause mortality, <0.001; hazard ratio [HR], 0.68; 0.57-0.81; =0.004; HR, 0.55; 0.37-0.83). Conclusion U.S. adults overall, while rate considerable trend. Both showed marked differences, being at risk compared men. It important identify factors that will curb decrease especially male patients.

Язык: Английский

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The bioavailability, absorption, metabolism, and regulation of glucolipid metabolism disorders by quercetin and its important glycosides: A review

Food Chemistry, Год журнала: 2024, Номер 458, С. 140262 - 140262

Опубликована: Июнь 27, 2024

Язык: Английский

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Pathways in formulating foods for the elderly

Food Research International, Год журнала: 2024, Номер 186, С. 114324 - 114324

Опубликована: Апрель 17, 2024

The growth of the elderly population worldwide is posing significant challenges to human society. progressive physical and physiological changes occur with aging, including decreased appetite, incomplete digestion, reduced absorption nutrients. A common feature many people's diets a deficiency in proteins (especially easily digestible ones) micronutrients (e.g., vitamins, zinc, iron, calcium). One solutions this problem incorporation these components into suitably texture-modified foods. There dearth products that meet needs special medical/health conditions such as dysphagia, osteoporosis, diabetes, cardiovascular disease, well those who are hospital palliative care. Future research development foods for must address specific dietary different subgroups people underlying health conditions. existence stages means their requirements be considered. This review summarizes current knowledge on nutritional problems outlines innovation pathways developing new considering nutrition, texture, flavor, other sensory aspects.

Язык: Английский

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The solute carrier transporters and the brain: Physiological and pharmacological implications

Asian Journal of Pharmaceutical Sciences, Год журнала: 2019, Номер 15(2), С. 131 - 144

Опубликована: Ноя. 13, 2019

Solute carriers (SLCs) are the largest family of transmembrane transporters that determine exchange various substances, including nutrients, ions, metabolites, and drugs across biological membranes. To date, presence about 287 SLC genes have been identified in brain, among which mutations or resultant dysfunctions 71 reported to be correlated with human brain disorders. Although increasing interest SLCs focused on drug development, currently still under-explored as targets, especially brain. We summarize main substrates functions expressed an emphasis selected important physiologically, pathologically, pharmacologically blood-brain barrier, astrocytes, neurons. Evidence suggests a fraction regulated along occurrences disorders, epilepsy, neurodegenerative diseases, autism representative. Given review involved onset procession we hope these will screened promising targets improve delivery

Язык: Английский

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