Iron, glucose and fat metabolism and obesity: an intertwined relationship

Hilton, Catriona; Sabaratnam, Rugivan; Drakesmith, Hal; Karpe, Fredrik

doi:10.1038/s41366-023-01299-0

Cited by 32 publications

(27 citation statements)

References 154 publications

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“…Iron is essential for several fundamental metabolic functions, including the transportation of oxygen. The risk of developing T2D has been found to be positively associated with iron overload and/ or the body iron stores most often measured as serum ferritin (65)(66)(67)(68)(69)(70). Serum ferritin is furthermore inversely associated with plasma adiponectin in a cohort of individuals with or at an increased risk of T2D and cardiovascular diseases (71,72).…”

Section: Discussionmentioning

confidence: 99%

High-throughput proteomics uncovers exercise training and type 2 diabetes–induced changes in human white adipose tissue

Larsen,

Kruse,

Sahebekhtiari

et al. 2023

Sci. Adv.

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White adipose tissue (WAT) is important for metabolic homeostasis. We established the differential proteomic signatures of WAT in glucose-tolerant lean and obese individuals and patients with type 2 diabetes (T2D) and the response to 8 weeks of high-intensity interval training (HIIT). Using a high-throughput and reproducible mass spectrometry–based proteomics pipeline, we identified 3773 proteins and found that most regulated proteins displayed progression in markers of dysfunctional WAT from lean to obese to T2D individuals and were highly associated with clinical measures such as insulin sensitivity and HbA1c. We propose that these distinct markers could serve as potential clinical biomarkers. HIIT induced only minor changes in the WAT proteome. This included an increase in WAT ferritin levels independent of obesity and T2D, and WAT ferritin levels were strongly correlated with individual insulin sensitivity. Together, we report a proteomic signature of WAT related to obesity and T2D and highlight an unrecognized role of human WAT iron metabolism in exercise training adaptations.

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Section: Discussionmentioning

confidence: 99%

High-throughput proteomics uncovers exercise training and type 2 diabetes–induced changes in human white adipose tissue

Larsen,

Kruse,

Sahebekhtiari

et al. 2023

Sci. Adv.

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“…Iron is redox-active and involved in reactions with oxygen radicals. Iron de ciency is a common cause of anemia, while iron overload can lead to oxidative stress and tissue damage, associated with multiple diseases such as MS, NAFLD, heart failure, neurodegenerative diseases, and cancer [20][21][22] . Therefore, maintaining iron homeostasis is crucial.…”

Section: Discussionmentioning

confidence: 99%

The effect of chronic intermittent hypobaric hypoxia improving liver damage in metabolic syndrome rats through ferritinophagy

Cui

Wang

et al. 2023

Preprint

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Background and aim Studies have confirmed that hepatic iron overload is one of the important factors causing liver damage in metabolic syndrome (MS). As a special form of autophagy, ferritinophagy is involved in the regulation of iron metabolism. Our previous studies have shown that chronic intermittent hypobaric hypoxia (CIHH) can improve the iron metabolism disorder. The aim of this study was to investigate how CIHH improves liver damage through ferritinophagy in rats with MS. Methods Male Sprague-Dawley rats aged 8–10 weeks were randomly divided into four groups: control (CON), CIHH (exposed to hypoxia at simulated altitude of 5000 meters for 28 days, 6 hours daily), MS model (induced by 16-week high fat diet and 10% fructose water feeding) and MS + CIHH (exposed to CIHH after 16-week MS inducement) groups. Liver index, liver function, iron content, tissue morphology, ferritinophagy, ferroptosis and iron metabolism related protein expression were measured, and the ferritinophagy flux in liver was further analyzed. Results Compared with CON rats, MS rats had increased liver index, damaged liver tissue morphology and function, increased total iron and free iron content, disrupted iron metabolism, significantly increased oxidative stress indicators in the liver, significantly increased expression of ferroptosis-related proteins, reduced expression of nuclear receptor coactivator 4 (NCOA4) and ferritinophagy flux. After CIHH treatment, the degree of liver damage and various abnormal indicators in MS rats were significantly improved. Conclusions CIHH may improve liver damage by promoting NCOA4-mediated ferritinophagy, reducing iron overload, and alleviating ferroptosis in MS rats.

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“…The effects we see in our analysis about association between iron and measures of carbohydrates may be mediated by the effect of iron on glycemic control via its impact on insulin sensitivity. Iron may play a role in the development of insulin resistance, as measures of iron have been shown to be associated with insulin sensitivity 65 . Existing literature also shows that glycemic dysregulation and related diseases are related to increased PD risk and worse PD outcomes [67][68][69] .…”

Section: Sugars and Carbohydratesmentioning

confidence: 99%

Dietary and Lifestyle Factors of Brain Iron Accumulation and Parkinson’s Disease Risk

Ahern,

Boyle,

Thompson

et al. 2024

Preprint

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Purpose: Iron is an essential nutrient which can only be absorbed through an individual's diet. Excess iron accumulates in organs throughout the body including the brain. Iron dysregulation in the brain is commonly associated with neurodegenerative diseases like Alzheimer's disease and Parkinson's Disease (PD). Our previous research has shown that a pattern of iron accumulation in motor regions of the brain related to a genetic iron-storage disorder called hemochromatosis is associated with an increased risk of PD. To understand how diet and lifestyle factors relate to this brain endophenotype and risk of PD we analyzed the relationship between these measures, estimates of nutrient intake, and diet and lifestyle preference using data from UK Biobank. Methods: Using distinct imaging and non-imaging samples (20,477 to 28,388 and 132,023 to 150,603 participants, respectively), we performed linear and logistic regression analyses using estimated dietary nutrient intake and food preferences to predict a) brain iron accumulation score (derived from T2-Weighted Magnetic Resonance Imaging) and b) PD risk. In addition, we performed a factor analysis of diet and lifestyle preferences to investigate if latent lifestyle factors explained significant associations. Finally, we performed an instrumental variable regression of our results related to iron accumulation and PD risk to identify if there were common dietary and lifestyle factors that were jointly associated with differences in brain iron accumulation and PD risk. Results: We found multiple highly significant associations with measures of brain iron accumulation and preferences for alcohol (factor 7: t=4.02, pFDR=0.0003), exercise (factor 11: t=-4.31, pFDR=0.0001), and high-sugar foods (factor 2: t=-3.73, pFDR=0.0007). Preference for alcohol (factor 7: t=-5.83, pFDR<1x10-8), exercise (factor 11: t=-7.66, pFDR<1x10-13), and high sugar foods (factor 2: t=6.03, pFDR<1x10-8) were also associated with PD risk. Instrumental variable regression of individual preferences revealed a significant relationship in which dietary preferences associated with higher brain iron levels also appeared to be linked to a lower risk for PD (p=0.004). A similar relationship was observed for estimates of nutrient intake (p=0.0006). Voxel-wise analysis of i) high-sugar and ii) alcohol factors confirmed T2-weighted signal differences consistent with iron accumulation patterns in motor regions of the brain including the cerebellum and basal ganglia. Conclusion: Dietary and lifestyle factors and preferences, especially those related to carbohydrates, alcohol, and exercise, are related to detectable differences in brain iron accumulation and alterations in risk of PD, suggesting a potential avenue for lifestyle interventions that could influence risk.

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Iron, glucose and fat metabolism and obesity: an intertwined relationship

Cited by 32 publications

References 154 publications

High-throughput proteomics uncovers exercise training and type 2 diabetes–induced changes in human white adipose tissue

High-throughput proteomics uncovers exercise training and type 2 diabetes–induced changes in human white adipose tissue

The effect of chronic intermittent hypobaric hypoxia improving liver damage in metabolic syndrome rats through ferritinophagy

Dietary and Lifestyle Factors of Brain Iron Accumulation and Parkinson’s Disease Risk

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