Does elevated bilirubin aid weight control by preventing development of hypothalamic leptin resistance?

DiNicolantonio, James J.; McCarty, Mark F.; O’Keefe, James H.

doi:10.1136/openhrt-2018-000897

Cited by 5 publications

(5 citation statements)

References 107 publications

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“…Several studies have shown that moderate levels of bilirubin are correlated with reduced abdominal obesity and a lower risk of metabolic syndrome [ 40 , 41 , 42 , 43 ]. Compared to wild-type mice, the body weight in the 9-months-old mice was significantly reduced in female but not in male Ugt1 −/− mice ( Figure S9A ).…”

Section: Resultsmentioning

confidence: 99%

Long-Term Effects of Biliverdin Reductase a Deficiency in Ugt1−/− Mice: Impact on Redox Status and Metabolism

et al. 2021

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Accumulation of neurotoxic bilirubin due to a transient neonatal or persistent inherited deficiency of bilirubin glucuronidation activity can cause irreversible brain damage and death. Strategies to inhibit bilirubin production and prevent neurotoxicity in neonatal and adult settings seem promising. We evaluated the impact of Bvra deficiency in neonatal and aged mice, in a background of unconjugated hyperbilirubinemia, by abolishing bilirubin production. We also investigated the disposal of biliverdin during fetal development. In Ugt1−/− mice, Bvra deficiency appeared sufficient to prevent lethality and to normalize bilirubin level in adults. Although biliverdin accumulated in Bvra-deficient fetuses, both Bvra−/− and Bvra−/−Ugt1−/− pups were healthy and reached adulthood having normal liver, brain, and spleen histology, albeit with increased iron levels in the latter. During aging, both Bvra−/− and Bvra−/−Ugt1−/− mice presented normal levels of relevant hematological and metabolic parameters. Interestingly, the oxidative status in erythrocytes from 9-months-old Bvra−/− and Bvra−/−Ugt1−/− mice was significantly reduced. In addition, triglycerides levels in these 9-months-old Bvra−/− mice were significantly higher than WT controls, while Bvra−/−Ugt1−/− tested normal. The normal parameters observed in Bvra−/−Ugt1−/− mice fed chow diet indicate that Bvra inhibition to treat unconjugated hyperbilirubinemia seems safe and effective.

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Section: Resultsmentioning

confidence: 99%

Long-Term Effects of Biliverdin Reductase a Deficiency in Ugt1−/− Mice: Impact on Redox Status and Metabolism

et al. 2021

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“…Интересно, что синдром Жильбера связан со снижением склонности к набору жира в более позднем возрасте [18,19]. Лица с синдромом Жильбера в более молодой возрастной группе имеют более низкий индекс массы тела (ИМТ) по сравнению с контрольной группой (22,5 против 23,5 кг/м 2 ), в то время как разница в старшей возрастной группе намного выше (23,8 против 27,2 кг/м 2 ).…”

Section: Liver Diseasesunclassified

“…Лица с синдромом Жильбера в более молодой возрастной группе имеют более низкий индекс массы тела (ИМТ) по сравнению с контрольной группой (22,5 против 23,5 кг/м 2 ), в то время как разница в старшей возрастной группе намного выше (23,8 против 27,2 кг/м 2 ). Соответственно, среднее содержание жира в организме у пожилых людей с синдромом Жильбера существенно ниже, чем у контрольной группы того же возраста [19]. Более высокие уровни билирубина в плазме связаны с лучшей чувствительностью к инсулину и более низким риском метаболического синдрома и диабета 2-го типа независимо от ИМТ [20,21].…”

Section: Liver Diseasesunclassified

“…То же самое справедливо и для защитной роли билирубина в развитии сосудистых диабетических осложнений [22]. Несмотря на то что билирубин помогает поддерживать чувствительность адипоцитов к инсулину (что теоретически должно приводить к поддержанию жировой ткани), он уменьшает ожирение, скорее всего, из-за его роли в предотвращении чувствительности гипоталамуса к лептину путем ингибирования активации микроглии [19]. Все эти факты могут объяснить более значительные положительные метаболические эффекты билирубина у людей с синдромом Жильбера старшего возраста, а также объяснить снижение общей смертности и увеличение продолжительности жизни людей с синдромом Жильбера [23,24].…”

Section: Liver Diseasesunclassified

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“Dark and bright sides” of Gilbert’s syndrome

Plotnikova,

Sinkova,

Isakov

2024

Medicinskij sovet

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Gilbert’s syndrome, also known as benign hyperbilirubinemia, was described more than 100 years ago. It has usually been considered a physiological abnormality characterized by a mild elevation of the systemic level of unconjugated bilirubin, in the absence of any underlying liver or overt RBC hemolysis. The molecular basis of Gilbert’s syndrome lies in the impairment of the conjugation of bilirubin with glucuronic acid in the hepatocytes, which is mediated by a specific hepatic enzyme named bilirubin-UDP-glucuronosyl transferase 1A1 that forms bilirubin diglucuronoside. Clearance of various xenobiotics, which are not substrates for glucuronosylation, is impaired in patients with Gilbert’s syndrome; their detailed list is provided in the article. Fatigue, asthenia, and various vaguely defined dyspeptic complaints attributed to Gilbert’s syndrome in the past are no longer considered a part of this condition, and proper evaluation of possible causes is required in these cases. Since the re-discovery of the potent antioxidant effects of bilirubin in the late 1980s, as well as the multiple intracellular signalling pathways affected by bilirubin, an ever-increasing body of evidence suggests that individuals with Gilbert’s syndrome may benefit from the mild hyperbilirubinemia and are actually protected from the development of a wide range of “diseases of civilization”, such as cardiovascular diseases, certain cancers, and autoimmune or neurodegenerative diseases. Gilbert’s syndrome is defined phenotypically, and therefore not according to predisposing genetic markers, as the elevation of serum unconjugated bilirubin concentration above the upper limit of normal, with no laboratory signs of hemolysis or liver damage. This review analyses the current state of medical knowledge given recent discoveries in this rapidly developing field, as well as their possible clinical significance, and provides a new perspective on this condition.

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“…S. platensis cell walls are made of liposaccharides that can induce the innate immune response through the toll-like receptor 4 (TLR-4) (McCarty et al 2010). Although S. platensis is a Gram-negative bacterium, it does not exhibit an antagonistic reaction towards TLR-4 due to its nature as a cyanobacterium (Okuyama et al 2017;DiNicolantonio et al 2019). However, other Gram-negative bacteria such as Salmonella do not tolerate TLR-4 reactions (Lima et al 2017).…”

Section: Nutritional Values Osf Spirulinamentioning

confidence: 99%

Impact of Metallic Nanoparticles on the Nutritional Values of Spirulina

et al. 2022

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Spirulina has high nutritional values and anti-oxidative properties. It is a staple diet due to its easy cultivation and greater nutritional values in biological macromolecules (proteins, lipids, and carbohydrates), pigments (chlorophyll, carotenoids, phycobiliproteins) vitamins, minerals, phenolic compounds, and amino acids. Spirulina also has been used as a nutraceutical to treat numerous diseases and disorders due to its promising therapeutic values. However, extensive anthropogenic activities cause the discharge of metals and metallic nanoparticles into the environment that might cause toxicity to marine and freshwater microalgae due to bioaccumulation. The presence of metals in the environment beyond the normal range does not only affect the growth but also the nutritional values of microalgae. The nutritional properties and usage of Spirulina along with the harmful effects of metals and metallic nanoparticles on Spirulina are highlighted and summarized in this paper.

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Does elevated bilirubin aid weight control by preventing development of hypothalamic leptin resistance?

Cited by 5 publications

References 107 publications

Long-Term Effects of Biliverdin Reductase a Deficiency in Ugt1−/− Mice: Impact on Redox Status and Metabolism

Long-Term Effects of Biliverdin Reductase a Deficiency in Ugt1−/− Mice: Impact on Redox Status and Metabolism

“Dark and bright sides” of Gilbert’s syndrome

Impact of Metallic Nanoparticles on the Nutritional Values of Spirulina

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