Observational studies have shown that dietary fiber intake is associated with decreased risk of cardiovascular disease. Dietary fiber is a non-digestible form of carbohydrates, due to the lack of the digestive enzyme in humans required to digest fiber. Dietary fibers and lignin are intrinsic to plants and are classified according to their water solubility properties as either soluble or insoluble fibers. Water-soluble fibers include pectin, gums, mucilage, fructans, and some resistant starches. They are present in some fruits, vegetables, oats, and barley. Soluble fibers have been shown to lower blood cholesterol by several mechanisms. On the other hand, water-insoluble fibers mainly include lignin, cellulose, and hemicellulose; whole-grain foods, bran, nuts, and seeds are rich in these fibers. Water-insoluble fibers have rapid gastric emptying, and as such may decrease the intestinal transit time and increase fecal bulk, thus promoting digestive regularity. In addition to dietary fiber, isolated and extracted fibers are known as functional fiber and have been shown to induce beneficial health effects when added to food during processing. The recommended daily allowances (RDAs) for total fiber intake for men and women aged 19–50 are 38 gram/day and 25 gram/day, respectively. It is worth noting that the RDA recommendations are for healthy people and do not apply to individuals with some chronic diseases. Studies have shown that most Americans do not consume the recommended intake of fiber. This review will summarize the current knowledge regarding dietary fiber, sources of food containing fiber, atherosclerosis, and heart disease risk reduction.
The rapamycin-sensitive mTOR complex 1 (mTORC1) promotes protein synthesis, cell growth, and cell proliferation in response to growth factors and nutritional cues. To elucidate the poorly defined mechanisms underlying mTORC1 regulation, we have studied the phosphorylation of raptor, an mTORinteracting partner. We have identified six raptor phosphorylation sites that lie in two centrally localized clusters (
The mammalian target of rapamycin (mTOR) Ser/Thr kinase signals in at least two multiprotein complexes distinguished by their different partners and sensitivities to rapamycin. Acute rapamycin inhibits signaling by mTOR complex 1 (mTORC1) but not mTOR complex 2 (mTORC2), which both promote cell growth, proliferation, and survival. Although mTORC2 regulation remains poorly defined, diverse cellular mitogens activate mTORC1 signaling in a manner that requires sufficient levels of amino acids and cellular energy. Before the identification of distinct mTOR complexes, mTOR was reported to autophosphorylate on Ser-2481 in vivo in a rapamycin-and amino acid-insensitive manner. These results suggested that modulation of mTOR intrinsic catalytic activity does not universally underlie mTOR regulation. Here we re-examine the regulation of mTOR Ser-2481 autophosphorylation (Ser(P)-2481) in vivo by studying mTORC-specific Ser(P)-2481 in mTORC1 and mTORC2, with a primary focus on mTORC1. In contrast to previous work, we find that acute rapamycin and amino acid withdrawal markedly attenuate mTORC1-associated mTOR Ser(P)-2481 in cycling cells. Although insulin stimulates both mTORC1-and mTORC2-associated mTOR Ser(P)-2481 in a phosphatidylinositol 3-kinase-dependent manner, rapamycin acutely inhibits insulin-stimulated mTOR Ser(P)-2481 in mTORC1 but not mTORC2. By interrogating diverse mTORC1 regulatory input, we find that without exception mTORC1-activating signals promote, whereas mTORC1-inhibitory signals decrease mTORC1-associated mTOR Ser(P)-2481. These data suggest that mTORC1-and likely mTORC2-associated mTOR Ser-2481 autophosphorylation directly monitors intrinsic mTORC-specific catalytic activity and reveal that rapamycin inhibits mTORC1 signaling in vivo by reducing mTORC1 catalytic activity.
The mammalian target of rapamycin (mTOR) complex 1 (mTORC1) functions as a rapamycin-sensitive environmental sensor that promotes cellular biosynthetic processes in response to growth factors and nutrients. While diverse physiological stimuli modulate mTORC1 signaling, the direct biochemical mechanisms underlying mTORC1 regulation remain poorly defined. Indeed, while three mTOR phosphorylation sites have been reported, a functional role for site-specific mTOR phosphorylation has not been demonstrated. Here we identify a new site of mTOR phosphorylation (S1261) by tandem mass spectrometry and demonstrate that insulin-phosphatidylinositol 3-kinase signaling promotes mTOR S1261 phosphorylation in both mTORC1 and mTORC2. Here we focus on mTORC1 and show that TSC/Rheb signaling promotes mTOR S1261 phosphorylation in an amino acid-dependent, rapamycin-insensitive, and autophosphorylation-independent manner. Our data reveal a functional role for mTOR S1261 phosphorylation in mTORC1 action, as S1261 phosphorylation promotes mTORC1-mediated substrate phosphorylation (e.g., p70 ribosomal protein S6 kinase 1 [S6K1] and eukaryotic initiation factor 4E binding protein 1) and cell growth to increased cell size. Moreover, Rheb-driven mTOR S2481 autophosphorylation and S6K1 phosphorylation require S1261 phosphorylation. These data provide the first evidence that site-specific mTOR phosphorylation regulates mTORC1 function and suggest a model whereby insulin-stimulated mTOR S1261 phosphorylation promotes mTORC1 autokinase activity, substrate phosphorylation, and cell growth.
Cardiovascular disease (CVD) is the leading cause of death in the United States. For years, dietary cholesterol was implicated in increasing blood cholesterol levels leading to the elevated risk of CVD. To date, extensive research did not show evidence to support a role of dietary cholesterol in the development of CVD. As a result, the 2015–2020 Dietary Guidelines for Americans removed the recommendations of restricting dietary cholesterol to 300 mg/day. This review summarizes the current literature regarding dietary cholesterol intake and CVD. It is worth noting that most foods that are rich in cholesterol are also high in saturated fatty acids and thus may increase the risk of CVD due to the saturated fatty acid content. The exceptions are eggs and shrimp. Considering that eggs are affordable and nutrient-dense food items, containing high-quality protein with minimal saturated fatty acids (1.56 gm/egg) and are rich in several micronutrients including vitamins and minerals, it would be worthwhile to include eggs in moderation as a part of a healthy eating pattern. This recommendation is particularly relevant when individual’s intakes of nutrients are suboptimal, or with limited income and food access, and to help ensure dietary intake of sufficient nutrients in growing children and older adults.
The mechanistic Target of Rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase which is a member of the PI3K related kinase (PIKK) family. mTOR emerged as a central node in cellular metabolism, cell growth, and differentiation, as well as cancer metabolism. mTOR senses the nutrients, energy, insulin, growth factors, and environmental cues and transmits signals to downstream targets to effectuate the cellular and metabolic response. Recently, mTOR was also implicated in the regulation of both the innate and adaptive immune responses. This paper will summarize the current knowledge of mTOR, as related to the immune microenvironment and immune responses.
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