Metabolic Syndrome Pathophysiology

Das, Undurti N.

doi:10.1002/9780813820637

Cited by 38 publications

(5 citation statements)

References 87 publications

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“…All these abnormalities could be ameliorated by supplementing these C. elegans with diet rich in GLA or AA or EPA [ 171 , 172 ]. These and several other studies attest to the fact that BALs are needed for various functions such as growth and development (especially of brain), neurotransmission, behavior, circadian rhythm, reproduction, immune response, to prevent high-glucose-induced life-span reduction, regulation of obesity, and several other features that are essential for normal life span [ 171 , 172 , 173 , 174 ], implying that one of the critical functions of BALs could be to regulate aging and aging associated disorders including obesity, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, Alzheimer’s disease, depression, and cancer [ 23 , 58 , 117 , 155 , 175 , 176 , 177 ]. These results are in tune with the observation that patients with type 2 DM, hypertension, coronary heart disease, cancer, lupus, RA and pneumonia have altered PUFA metabolism [ 155 ] (see Table 3 , Table 4 and Table 5 ).…”

Section: Aa In C Elegans and Life Spanmentioning

confidence: 99%

“…It is noteworthy that PGs of 2 series, TXs of 2 series and LTs of 4 series derived from AA are more pro-inflammatory in nature compared to those formed from EPA (3 series PGs and TXs and 5 series LTs are from EPA). Plasma and tissue levels of PGE2 are elevated in many inflammatory conditions {reviewed in [ 23 , 30 , 41 , 42 , 175 , 176 , 177 ]}. It is known that once the inflammatory process reaches its peak and so also the local concentrations of PGE2, the metabolism of AA is redirected to form LXA4 to trigger inflammation resolution process.…”

Section: Conclusion and Therapeutic Implicationsmentioning

confidence: 99%

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“Cell Membrane Theory of Senescence” and the Role of Bioactive Lipids in Aging, and Aging Associated Diseases and Their Therapeutic Implications

Das

2021

Biomolecules

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Lipids are an essential constituent of the cell membrane of which polyunsaturated fatty acids (PUFAs) are the most important component. Activation of phospholipase A2 (PLA2) induces the release of PUFAs from the cell membrane that form precursors to both pro- and ant-inflammatory bioactive lipids that participate in several cellular processes. PUFAs GLA (gamma-linolenic acid), DGLA (dihomo-GLA), AA (arachidonic acid), EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are derived from dietary linoleic acid (LA) and alpha-linolenic acid (ALA) by the action of desaturases whose activity declines with age. Consequently, aged cells are deficient in GLA, DGLA, AA, AA, EPA and DHA and their metabolites. LA, ALA, AA, EPA and DHA can also be obtained direct from diet and their deficiency (fatty acids) may indicate malnutrition and deficiency of several minerals, trace elements and vitamins some of which are also much needed co-factors for the normal activity of desaturases. In many instances (patients) the plasma and tissue levels of GLA, DGLA, AA, EPA and DHA are low (as seen in patients with hypertension, type 2 diabetes mellitus) but they do not have deficiency of other nutrients. Hence, it is reasonable to consider that the deficiency of GLA, DGLA, AA, EPA and DHA noted in these conditions are due to the decreased activity of desaturases and elongases. PUFAs stimulate SIRT1 through protein kinase A-dependent activation of SIRT1-PGC1α complex and thus, increase rates of fatty acid oxidation and prevent lipid dysregulation associated with aging. SIRT1 activation prevents aging. Of all the SIRTs, SIRT6 is critical for intermediary metabolism and genomic stability. SIRT6-deficient mice show shortened lifespan, defects in DNA repair and have a high incidence of cancer due to oncogene activation. SIRT6 overexpression lowers LDL and triglyceride level, improves glucose tolerance, and increases lifespan of mice in addition to its anti-inflammatory effects at the transcriptional level. PUFAs and their anti-inflammatory metabolites influence the activity of SIRT6 and other SIRTs and thus, bring about their actions on metabolism, inflammation, and genome maintenance. GLA, DGLA, AA, EPA and DHA and prostaglandin E2 (PGE2), lipoxin A4 (LXA4) (pro- and anti-inflammatory metabolites of AA respectively) activate/suppress various SIRTs (SIRt1 SIRT2, SIRT3, SIRT4, SIRT5, SIRT6), PPAR-γ, PARP, p53, SREBP1, intracellular cAMP content, PKA activity and peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1-α). This implies that changes in the metabolism of bioactive lipids as a result of altered activities of desaturases, COX-2 and 5-, 12-, 15-LOX (cyclo-oxygenase and lipoxygenases respectively) may have a critical role in determining cell age and development of several aging associated diseases and genomic stability and gene and oncogene activation. Thus, methods designed to maintain homeostasis of bioactive lipids (GLA, DGLA, AA, EPA, DHA, PGE2, LXA4) may arrest aging process and associated metabolic abnormalities.

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Section: Aa In C Elegans and Life Spanmentioning

confidence: 99%

Section: Conclusion and Therapeutic Implicationsmentioning

confidence: 99%

“Cell Membrane Theory of Senescence” and the Role of Bioactive Lipids in Aging, and Aging Associated Diseases and Their Therapeutic Implications

Das

2021

Biomolecules

Self Cite

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“…DHA also attenuated Ab secretion, enhanced neuroprotectin synthesis, which represses inflammation, oxidative stress, and cell apoptosis induced by Ab 42, and thus promoted neuronal survival [115]. Fish oil dietary supplementation, a rich source of u-3, exerts neuron-protective function in diabetic rats through antiapoptotic pathways and significantly improved the ability of learning and memory [116][117][118].…”

Section: Docosahexaenoic Acidmentioning

confidence: 99%

Cognitive and motor perturbations in elderly with longstanding diabetes mellitus

et al. 2014

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“…Moreover, oxidants can promote chromatin remodeling, which facilitates the expression of proinflammatory genes (Foronjy and D'Armiento, 2006). It is possible that low-grade chronic inflammation caused by cigarette smoking provides an inflammatory platform that may increase an individual's vulnerability to other risk factors such as diet (Das, 2010). In this study, when food group intake was assessed separated by smokers and nonsmokers, nonstarchy vegetables were observed to be protective against PC in nonsmokers individuals.…”

Section: Discussionmentioning

confidence: 68%

Tobacco smoking patterns and differential food effects on prostate and breast cancers among smokers and nonsmokers in Córdoba, Argentina

Román¹,

Niclis

Tumas

et al. 2014

European Journal of Cancer Prevention

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The aim of this study was to estimate the effect of diet on prostate and breast cancer (PC and BC) risks in smokers and nonsmokers and to explore the effect modification between smoking and dietary patterns. PC or BC incidence rates were assessed spatially according to tobacco exposure, age-adjusted standardization using lung cancer mortality as a proxy. Two case-control studies were carried out in Argentina (2008-2012). Participants were interviewed about their diet, smoking habits, and other lifestyle factors. Multilevel models were fitted including family history of cancer as the random intercept for the second level, and diet and lifestyle variables as covariates. Tobacco exposure was aggregated spatially. Family history of cancer significantly accounts for PC and BC. In smokers, high intake of fat meat increased PC and BC risks [odds ratio (OR) 1.56, 95% confidence interval (CI) 0.81-3.05 and OR 6.01, 95% CI 1.99-8.19, respectively]. PC and BC risks were also greater in smokers with high intakes of fatty foods (OR 1.95, 95% CI 1.09-3.50 and OR 24.2, 95% CI 0.82-7.21, respectively). Moderate intake of nonstarchy vegetables and risk of PC were inversely associated in nonsmokers (OR 0.55, 95% CI 0.20-1.48). In smoker women, BC risk was associated with sweet drink consumption (OR 2.96, 95% CI 1.10-7.92) and ethanol intake (OR 5.15, 95% CI 1.88-14.16). Spatial distributions of cancer incidence rates match those of tobacco exposure. Differential effects of diet on PC and BC risks were found in smokers and nonsmokers.

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Metabolic Syndrome Pathophysiology

Cited by 38 publications

References 87 publications

“Cell Membrane Theory of Senescence” and the Role of Bioactive Lipids in Aging, and Aging Associated Diseases and Their Therapeutic Implications

“Cell Membrane Theory of Senescence” and the Role of Bioactive Lipids in Aging, and Aging Associated Diseases and Their Therapeutic Implications

Cognitive and motor perturbations in elderly with longstanding diabetes mellitus

Tobacco smoking patterns and differential food effects on prostate and breast cancers among smokers and nonsmokers in Córdoba, Argentina

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