scholarly journals Mitochondrial Genome Variation and Metabolic Traits in a Maori Community

2021 ◽  
Author(s):  
◽  
Miles Clifford Benton

<p>The mitochondrion is the energy producing factory of cells and it has long been thought that disruption to mitochondrial systems is linked to energy metabolism dysfunction. Sequence variants in the mitochondrial genome are plausible candidate risk factors for numerous human diseases, and research has identified specific mitochondrial DNA (mtDNA) variants associated with metabolic disorders such as obesity and type-2 diabetes. As part of the Rakaipaaka Health and Ancestry Study (RHAS) it has been observed that the Maori community of Nuhaka (Ngati Rakaipaaka) have a high incidence of certain metabolic diseases, namely obesity and diabetes. The reason for this is not well understood, but is likely to be a combination of both current lifestyle (e.g. dietary) and ancestral genetic factors. This study set out to sequence the entire mitochondrial genome in a sample of RHAS Maori participants. The aim was to discover genetic variation that might be specific to this Maori community and test whether such variants are associated with diabetes and other metabolic traits. This study used a novel RFLP assay to screen the mtDNA control region for Polynesian mtDNA ancestry. This established an initial group (n=30) with high levels of Maori mtDNA. Hypervariable (HVRI) sequencing was then used to generate a large dataset of sequences (n=94). This dataset was representative of individuals showing high Maori ancestry and aided the selection of 20 mtDNA's for Mitochip analysis. Combining the RHAS Maori HVRI sequences with those from previous studies indicated elevated variation in Maori mtDNA. Haplotype analysis identified 17 unique Maori haplotypes, 10 more than previously recorded. Mitochip resequencing has provided the first complete Maori mtDNA sequences to date. When compared to other mtDNA sequences it was identified that RHAS Maori share similar haplotype markers with Polynesians. Seven novel undocumented variants were found, as well as four variants that had previously been associated with various metabolic disorders. Mitochip analysis of mtDNA sequences revealed three variants which created a RHAS Maori specific signature; C1185T, G4769A, and T16126C. These variants also defined 3 unique mtDNA haplotypes within RHAS Maori, which are the first Maori specific haplotypes reported. Variant genotyping and correlation with metabolic traits identified significant associations within the wider RHAS Maori community. It was identified that RHAS Maori with T16189C showed elevation in both vitamin B12 levels and mean diastolic blood pressure. Individuals with the G4769A variant were shown to have significant increases in specific metabolic risk factors for cardiovascular disease. Conversely individuals with the more common A4769G variant were 2 times less likely to be diagnosed with diabetes. The findings from this study have identified a series of potential markers of metabolic disease within the RHAS Maori community. The goal now is to understand how these markers interact with environmental variables to increase the risk of metabolic syndrome. Such an outcome may open the way to designing personalised intervention strategies (e.g. dietary) to increase the health and well-being of at risk individuals.</p>

2021 ◽  
Author(s):  
◽  
Miles Clifford Benton

<p>The mitochondrion is the energy producing factory of cells and it has long been thought that disruption to mitochondrial systems is linked to energy metabolism dysfunction. Sequence variants in the mitochondrial genome are plausible candidate risk factors for numerous human diseases, and research has identified specific mitochondrial DNA (mtDNA) variants associated with metabolic disorders such as obesity and type-2 diabetes. As part of the Rakaipaaka Health and Ancestry Study (RHAS) it has been observed that the Maori community of Nuhaka (Ngati Rakaipaaka) have a high incidence of certain metabolic diseases, namely obesity and diabetes. The reason for this is not well understood, but is likely to be a combination of both current lifestyle (e.g. dietary) and ancestral genetic factors. This study set out to sequence the entire mitochondrial genome in a sample of RHAS Maori participants. The aim was to discover genetic variation that might be specific to this Maori community and test whether such variants are associated with diabetes and other metabolic traits. This study used a novel RFLP assay to screen the mtDNA control region for Polynesian mtDNA ancestry. This established an initial group (n=30) with high levels of Maori mtDNA. Hypervariable (HVRI) sequencing was then used to generate a large dataset of sequences (n=94). This dataset was representative of individuals showing high Maori ancestry and aided the selection of 20 mtDNA's for Mitochip analysis. Combining the RHAS Maori HVRI sequences with those from previous studies indicated elevated variation in Maori mtDNA. Haplotype analysis identified 17 unique Maori haplotypes, 10 more than previously recorded. Mitochip resequencing has provided the first complete Maori mtDNA sequences to date. When compared to other mtDNA sequences it was identified that RHAS Maori share similar haplotype markers with Polynesians. Seven novel undocumented variants were found, as well as four variants that had previously been associated with various metabolic disorders. Mitochip analysis of mtDNA sequences revealed three variants which created a RHAS Maori specific signature; C1185T, G4769A, and T16126C. These variants also defined 3 unique mtDNA haplotypes within RHAS Maori, which are the first Maori specific haplotypes reported. Variant genotyping and correlation with metabolic traits identified significant associations within the wider RHAS Maori community. It was identified that RHAS Maori with T16189C showed elevation in both vitamin B12 levels and mean diastolic blood pressure. Individuals with the G4769A variant were shown to have significant increases in specific metabolic risk factors for cardiovascular disease. Conversely individuals with the more common A4769G variant were 2 times less likely to be diagnosed with diabetes. The findings from this study have identified a series of potential markers of metabolic disease within the RHAS Maori community. The goal now is to understand how these markers interact with environmental variables to increase the risk of metabolic syndrome. Such an outcome may open the way to designing personalised intervention strategies (e.g. dietary) to increase the health and well-being of at risk individuals.</p>


2019 ◽  
Vol 317 (6) ◽  
pp. E1205-E1217 ◽  
Author(s):  
Siyuan Cui ◽  
Lu Qiao ◽  
Shanshan Yu ◽  
Lili Men ◽  
Yu Li ◽  
...  

Interleukin-8 (IL-8, also named CXCL8) binds to its receptors (CXCR1 and CXCR2) with subsequent recruitment of neutrophils and enhancement of their infiltration into inflamed sites, which exaggerates inflammation in many diseases. Recent studies have proposed that metabolic disorders can be attenuated by counteracting certain inflammatory signal pathways. In this study, we examined whether intervention with G31P, an antagonist of CXCL8, could attenuate tissue inflammation and development of metabolic disorders in db/db mice. The db/m and db/db mice were subcutaneously injected with G31P or equivalent normal saline once a day for 6 wk. The physical and metabolic parameters, glucose tolerance, insulin sensitivity, hepatic lipid accumulation, and inflammation markers were measured. G31P improved hepatic insulin sensitivity by modulating expression of genes related to gluconeogenesis and phosphorylated Akt levels. The expressions of several genes encoding proteins involved in de novo lipogenesis were decreased in G31P-treated db/db mice. Meanwhile, immune cell infiltration and cytokine release were attenuated in db/db mice with G31P treatment. G31P also improved the ratio of proinflammatory M1 and anti-inflammatory M2 macrophages. Furthermore, G31P ameliorates metabolic disturbances via inhibition of CXCR1 and CXCR2 pathways in db/db mice. These data suggest that the selective inhibition of CXC chemokines may have therapeutic effects on symptoms associated with obesity and diabetes.


2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Weilei Yao ◽  
Tongxin Wang ◽  
Feiruo Huang

The overwhelming frequency of metabolic diseases such as obesity and diabetes are closely related to liver diseases, which might share common pathogenic signaling processes. These metabolic disorders in the presence of inflammatory response seem to be triggered by and to reside in the liver, which is the central metabolic organ that plays primary roles in regulating lipid and glucose homeostasis upon alterations of metabolic conditions. Recently, abundant emerging researches suggested that p300 and CREB binding protein (CBP) are crucial regulators of energy homeostasis and liver fibrosis through both their acetyltransferase activities and transcriptional coactivators. Plenty of recent findings demonstrated the potential roles of p300/CBP in mammalian metabolic homeostasis in response to nutrients. This review is focused on the different targets and functions of p300/CBP in physiological and pathological processes, including lipogenesis, lipid export, gluconeogenesis, and liver fibrosis, also provided some nutrients as the regulator of p300/CBP for nutritional therapeutic approaches to treat liver diseases.


Author(s):  
Vera K. Tsenkova ◽  
Deborah Carr ◽  
Christopher L. Coe ◽  
Arun S. Karlamangla ◽  
Carol D. Ryff

Type 2 diabetes is a significant problem worldwide, accounting for substantial morbidity and premature mortality. Understanding why some people remain healthy while others progress to insulin resistance and diabetes requires an integrative approach. Models of diabetes have focused on excess weight and physical inactivity as key targets for reducing diabetes risk. Obesity is a risk factor for developing Type 2 diabetes, yet most obese persons do not develop diabetes, suggesting moderation by other influences. This chapter highlights Midlife in the United States studies that employed multidomain assessments of the interplay between established risk factors and psychosocial influences on diabetes. The chapter reviews evidence that depression, anger, perceived weight discrimination, and neuroticism exacerbate the association between obesity and diabetes. The conclusion that psychosocial processes are major risk factors underscores the need for assessing mental health and promoting psychological well-being to complement traditional prevention efforts.


Crisis ◽  
2016 ◽  
Vol 37 (2) ◽  
pp. 130-139 ◽  
Author(s):  
Danica W. Y. Liu ◽  
A. Kate Fairweather-Schmidt ◽  
Richard Burns ◽  
Rachel M. Roberts ◽  
Kaarin J. Anstey

Abstract. Background: Little is known about the role of resilience in the likelihood of suicidal ideation (SI) over time. Aims: We examined the association between resilience and SI in a young-adult cohort over 4 years. Our objectives were to determine whether resilience was associated with SI at follow-up or, conversely, whether SI was associated with lowered resilience at follow-up. Method: Participants were selected from the Personality and Total Health (PATH) Through Life Project from Canberra and Queanbeyan, Australia, aged 28–32 years at the first time point and 32–36 at the second. Multinomial, linear, and binary regression analyses explored the association between resilience and SI over two time points. Models were adjusted for suicidality risk factors. Results: While unadjusted analyses identified associations between resilience and SI, these effects were fully explained by the inclusion of other suicidality risk factors. Conclusion: Despite strong cross-sectional associations, resilience and SI appear to be unrelated in a longitudinal context, once risk/resilience factors are controlled for. As independent indicators of psychological well-being, suicidality and resilience are essential if current status is to be captured. However, the addition of other factors (e.g., support, mastery) makes this association tenuous. Consequently, resilience per se may not be protective of SI.


2013 ◽  
Vol 25 (3) ◽  
pp. 118-128 ◽  
Author(s):  
Florian Rehbein ◽  
Dirk Baier

In recent years, a variety of epidemiological studies have provided empirical data on the prevalence of video game addiction (GA) in different age groups. However, few studies investigated the causes of GA and could explain why video game playing as a widespread phenomenon leads to a comparatively small percentage of addicted players. Additionally, the existing longitudinal studies mainly consider psychological trait variables and neglect the possible explanatory value of predictors in socialization regarding media availability, media use, and family and everyday school life. In this paper, the results of a two-wave longitudinal study comprising a sample of students from Grades 4 to 9 (N = 406) are presented. The data show that 15-year-old video game addicts had already exhibited a number of specific risk factors at the age of 10. Students from single-parent families seem to be particularly at risk, as are students with low experienced school well-being and with a weaker social integration in class. The data also indicate that problematic use of video games in childhood increases the risk of GA in adolescence. Male students are especially vulnerable for developing GA. The results of this study are an important contribution to understanding risk factors for GA in adolescents, thereby laying the groundwork for effective prevention measures.


2018 ◽  
Vol 24 (23) ◽  
pp. 2729-2742 ◽  
Author(s):  
Nasrin Sharifi ◽  
Reza Tabrizi ◽  
Mahmood Moosazadeh ◽  
Naghmeh Mirhosseini ◽  
Kamran B. Lankarani ◽  
...  

Background and objective: Oxidative stress and inflammation are key parameters in developing metabolic disorders. Hence, antioxidant intake might be an appropriate approach. Several studies have evaluated the effect of coenzyme Q10 (CoQ10) supplementation on lipid profile among patients with metabolic diseases, though findings are controversial. The aim of this systematic review and meta-analysis was to determine the effects of CoQ10 supplementation on lipid profile in patients with metabolic disorders. Methods: We searched PubMed, EMBASE, Web of Science and Cochrane Library databases until July 2017. Prospective clinical trials were selected assessing the effect of CoQ10 supplementation on different biomarkers. Two reviewers independently assessed the eligibility of studies, extracted data, and evaluated the risk of bias of included studies. A fixed- or random-effects model was used to pool the data, which expressed as a standardized mean difference with 95% confidence interval. Heterogeneity was measured using a Q-test and with I2 statistics. Results: A total of twenty-one controlled trials (514 patients and 525 controls) were included. The meta-analysis indicated a significant reduction in serum triglycerides levels (SMD -0.28; 95% CI, -0.56, -0.005). CoQ10 supplementation also decreased total-cholesterol (SMD -0.07; 95% CI, -0.45, 0.31), increased LDL- (SMD 0.04; 95% CI, -0.27, 0.36), and HDL-cholesterol levels (SMD 0.10; 95% CI, -0.32, 0.51), not statistically significant. Conclusion: CoQ10 supplementation may significantly reduce serum triglycerides levels, and help to improve lipid profiles in patients with metabolic disorders. Additional prospective studies are recommended using higher supplementation doses and longer intervention period.


2009 ◽  
Vol 29 (2_suppl) ◽  
pp. 145-148 ◽  
Author(s):  
Paulo Cezar Fortes ◽  
Thyago Proença de Moraes ◽  
Jamille Godoy Mendes ◽  
Andrea E. Stinghen ◽  
Silvia Carreira Ribeiro ◽  
...  

Cardiovascular disease (CVD) is the main cause of death in peritoneal dialysis (PD) patients, a situation that can be explained by a combination of traditional and nontraditional risk factors for CVD in these patients. Glucose and insulin homeostasis are altered in chronic kidney disease (CKD) patients even in the early stages of CKD, leading to insulin resistance by various pathways. Several factors have been implicated in the pathogenesis of insulin resistance, including anemia, dyslipidemia, uremia, malnutrition, excess of parathyroid hormone, vitamin D deficiency, metabolic acidosis, and increase in plasma free fatty acids and proinflammatory cytokines. Insulin resistance and dyslipidemia are observed and increase with the progression of CKD, playing an important role in the pathogenesis of hypertension and atherosclerosis. Particularly in PD patients, exposure to glucose from dialysis fluid accentuates the foregoing metabolic abnormalities. In conclusion, insulin resistance and altered glucose metabolism are frequently observed in CKD, and although dialysis partly corrects those disturbances, the use of glucose PD solutions intensifies a series of harmful metabolic consequences. New therapeutic measures aimed at reducing metabolic disorders are urgently needed and perhaps will improve PD patient survival.


2021 ◽  
Vol 22 (3) ◽  
pp. 1317
Author(s):  
Hyun-Jeong Yang ◽  
Eugene Koh ◽  
Min-Kyu Sung ◽  
Hojung Kang

Studies have evidenced that epigenetic marks associated with type 2 diabetes (T2D) can be inherited from parents or acquired through fetal and early-life events, as well as through lifelong environments or lifestyles, which can increase the risk of diabetes in adulthood. However, epigenetic modifications are reversible, and can be altered through proper intervention, thus mitigating the risk factors of T2D. Mind–body intervention (MBI) refers to interventions like meditation, yoga, and qigong, which deal with both physical and mental well-being. MBI not only induces psychological changes, such as alleviation of depression, anxiety, and stress, but also physiological changes like parasympathetic activation, lower cortisol secretion, reduced inflammation, and aging rate delay, which are all risk factors for T2D. Notably, MBI has been reported to reduce blood glucose in patients with T2D. Herein, based on recent findings, we review the effects of MBI on diabetes and the mechanisms involved, including epigenetic modifications.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
T. Muhammad ◽  
Shobhit Srivastava ◽  
T. V. Sekher

Abstract Background Greater cognitive performance has been shown to be associated with better mental and physical health and lower mortality. The present study contributes to the existing literature on the linkages of self-perceived income sufficiency and cognitive impairment. Study also provides additional insights on other socioeconomic and health-related variables that are associated with cognitive impairment in older ages. Methods Data for this study is derived from the 'Building Knowledge Base on Population Ageing in India'. The final sample size for the analysis after removing missing cases was 9176 older adults. Descriptive along with bivariate analyses were presented to show the plausible associations of cognitive impairment with potential risk factors using the chi-square test. Also, binary logistic regression analysis was performed to provide the relationship between cognitive impairment and risk factors. The software used was STATA 14. Results About 43% of older adults reported that they had no source of income and 7.2% had income but not sufficient to fulfil their basic needs. Older adults with income but partially sufficient to fulfil their basic needs had 39% significantly higher likelihood to suffer from cognitive impairment than older adults who had sufficient income [OR: 1.39; OR: 1.21–1.59]. Likelihood of cognitive impairment was low among older adults with asset ownership than older adults with no asset ownership [OR: 0.83; CI: 0.72–0.95]. Again, older adults who work by compulsion (73.3%) or felt mental or physical stress due to work (57.6%) had highest percentage of cognitive impairment. Moreover, older adults with poor self-rated health, low instrumental activities of daily living, low activities of daily living, low subjective well-being and low psychological health were at increased risk for cognitive impairment. Conclusion The study highlights the pressing need for care and support and especially financial incentives in the old age to preserve cognitive health. Further, while planning geriatric health care for older adults in India, priority must be given to financially backward, with no asset ownership, with poor health status, older-older, widowed, and illiterate older individuals, as they are more vulnerable to cognitive impairment.


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