Markers of cholesterol synthesis are elevated in adolescents and young adults with type 2 diabetes

Semova, Ivana; Levenson, Amy; Krawczyk, Joanna; Bullock, Kevin; Williams, Kathryn; Wadwa, R. Paul; Khoury, Philip R.; Kimball, Thomas R.; Urbina, Elaine M.; Ferranti, Sarah D. de; Maahs, David M.; Dolan, Lawrence M.; Shah, Amy S.; Clish, Clary B.; Biddinger, Sudha B.

doi:10.1111/pedi.13097

Cited by 6 publications

(3 citation statements)

References 43 publications

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“…Cholesterol excessive accumulation resulted in beta-amyloid and decreased cholesterol synthesis led to synaptic defects. Epidemiological data indicated a correlation between evaluated serum cholesterol and diabetes and prolonged sleep deprivation in humans which is contrary to the results in the brain [44,45]. This apparent contradiction can be elucidated by the presence of the blood-brain barrier (BBB), which establishes plasma cholesterol and intracerebral cholesterol as distinct systems.…”

Section: Discussionmentioning

confidence: 89%

Trimethylamine N-oxide / SREBP2 pathway is involved in sleep deprivation-induced cognitive dysfunction through regulating astrocytic cholesterol metabolism

Zhu,

Wang,

et al. 2023

Preprint

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Sleep deprivation (SD) contributes to cognitive impairment. Astrocytic cholesterol biosynthesis is crucial for brain cholesterol homeostasis and cognitive function. However, the underlying mechanism of astrocytic cholesterol metabolism in SD-induced cognitive impairment has not been fully explored. Trimethylamine N-oxide (TMAO), a product of liver flavin-containing monooxygenase-3 (FMO3), has been shown to be increased in the urine of sleep-deprived humans and implicated with peripheral cholesterol metabolism. Nevertheless, how TMAO affects brain cholesterol metabolism remains unclear. In our study, increased FMO3 and brain TMAO levels were observed in the SD mice and elevated levels of TMAO were confirmed to lead to SD-induced cognitive dysfunction. In addition, we found that the expression of sterol regulatory element-binding protein 2 (SREBP2) is decreased in the brain of SD mice, resulting in the reduction in brain cholesterol synthesis, which in turn causes synaptic damage. Moreover, we demonstrated that TMAO inhibits the expression of SREBP2 by direct action. In contrast, FMO3 inhibitor 3,3'-diindolylmethane (DIM) alleviates SD-induced cognitive impairment by targeting the liver-brain axis. In conclusion, our study revealed that TMAO / SREBP2 pathway is involved in memory impairment in SD mice through deregulating astrocytic cholesterol metabolism.

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Section: Discussionmentioning

confidence: 89%

Trimethylamine N-oxide / SREBP2 pathway is involved in sleep deprivation-induced cognitive dysfunction through regulating astrocytic cholesterol metabolism

Zhu,

Wang,

et al. 2023

Preprint

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“…Body mass index and abdominal obesity were associated with at least one abnormal lipid level [29]. Cholesterol synthesis markers are higher in adolescents and young adults with type 2 diabetes than in lean subjects and are positively correlated with BMI, TG, hyperinsulinemia, hyperglycemia, and inflammation [30].…”

Section: Discussionmentioning

confidence: 98%

Association and Risk Factors for Hypertension and Dyslipidemia in Young Adults from Poland

Wyszyńska

Łuszczki

Sobek

et al. 2023

IJERPH

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Hypertension and dyslipidemia are major risk factors for cardiovascular disease. Studies on the association between abnormal levels of lipids and hypertension have yielded inconsistent results. The aim of this study was to examine the prevalence of hypertension and dyslipidemia and its risk factors in young Polish adults. Furthermore, the association between plasma lipid levels and the risk of hypertension was determined. A cross-sectional study was conducted among 115 volunteer participants. Blood pressure was measured using an automated oscillometric sphygmomanometer. Blood lipids were analyzed from a fasting blood sample received by finger prick. Body fat percentage was assessed using a bioelectrical impedance analysis device. Socioeconomic and lifestyle factors (age, date of birth, place of residence, screen time, and tobacco use) were self-reported by the participant. The prevalence of hypertension was higher in men than in women (61.5 vs. 21.3%). The prevalence of elevated TC, TG, high LDL, and low HDL was 22.6%, 7.8%, 38.3%, and 13.9%, respectively. Spending more than 2 h daily in front of a computer was identified as a significant predictor of hypertension and elevated TG levels (p < 0.05). A high number of cigarettes smoked daily was a significant risk factor for hypertension (p = 0.047). Hypertension contributed to a higher risk of abnormal values of TC (OR = 5.89), LDL (OR = 5.38), and TG (OR = 9.75). Participants with hypertension were more likely than normotensive subjects to have elevated levels of TC, LDL, and TG. The prevalence of hypertension was significantly higher in young men than in women. BMI was associated with the prevalence of hypertension and elevated TC levels. Spending more than 2 h per day in front of a computer contributed to the prevalence of hypertension and elevated TG levels. Participants with hypertension smoked a higher number of cigarettes daily compared to those with normotension.

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“…Some people had high absorption and some people had high synthesis. Other studies have shown that patients with type 2 diabetes and metabolic syndrome have high cholesterol synthesis [ 17 – 19 ], while patients with type 1 diabetes and familial hypercholesterolemia have high cholesterol absorption [ 20 – 22 ], further explaining the characteristics of individual differences in cholesterol absorption and synthesis.…”

Section: Discussionmentioning

confidence: 99%

Gas Chromatography and Flame-Ionization Detection of Non-Cholesterol Sterols as Indicators of Cholesterol Absorption and Synthesis in 158 Chinese Individuals with Normolipidemia, Hyperlipidemia, and Familial Hypercholesterolemia

Wang

Liu

et al. 2021

Med Sci Monit

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Background There are limited studies on the effects of cholesterol homeostasis in populations at high risk for cardiovascular disease. We aimed to use gas chromatography and flame-ionization detection (GC-FID) of non-cholesterol sterols as indicators of cholesterol absorption and synthesis. Sterol indicators of cholesterol absorption included campesterol, stigmasterol, and sitosterol. Sterol indicators of cholesterol synthesis included squalene, 7-lathosterol, and desmosterol. Material/Methods A total of 158 participants were enrolled in 3 groups: healthy control (n=64), hyperlipidemia (n=69), and familial hypercholesterolemia (FH, n=25). Age, sex, blood pressure, blood glucose, and lipoprotein were collected, and cholesterol absorption and synthesis markers were determined by GC-FID. Results All 6 cholesterol concentration indicators, except squalene, were significantly different among the 3 groups (all P <0.05); whereas in the ratio to cholesterol (%, sterols/cholesterol), only desmosterol and lathosterol were significantly different ( P <0.05). Multifactorial regression analysis showed that triglycerides, total cholesterol, and desmosterol were independent risk factors affecting the development of hyperlipidemia ( P <0.05). The efficacy of the ROC curve for the diagnosis of dyslipidemia was also higher for all 3 indices (Model 1, AUC=0.960). Model 1 was superior to Model 2 for the 6 indicators of cholesterol. For the FH and dyslipidemia groups, the 6-indicator model (Model 3) was shown to have a good diagnostic value (AUC=1.000). Conclusions The 6 sterol indicators of cholesterol absorption and synthesis had a dynamic course in all study participants. Desmosterol was an indicator of dyslipidemia. The combined use of the 6 sterol indicators differentiated between healthy individuals and patients with dyslipidemia and FH.

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Markers of cholesterol synthesis are elevated in adolescents and young adults with type 2 diabetes

Cited by 6 publications

References 43 publications

Trimethylamine N-oxide / SREBP2 pathway is involved in sleep deprivation-induced cognitive dysfunction through regulating astrocytic cholesterol metabolism

Trimethylamine N-oxide / SREBP2 pathway is involved in sleep deprivation-induced cognitive dysfunction through regulating astrocytic cholesterol metabolism

Association and Risk Factors for Hypertension and Dyslipidemia in Young Adults from Poland

Gas Chromatography and Flame-Ionization Detection of Non-Cholesterol Sterols as Indicators of Cholesterol Absorption and Synthesis in 158 Chinese Individuals with Normolipidemia, Hyperlipidemia, and Familial Hypercholesterolemia

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