Betaine Alleviates Hypertriglycemia and Tau Hyperphosphorylation in db/db Mice

Jung, Ga Young; Won, Sungjun; Kim, Juhae; Jeon, Sookyoung; Han, Anna; Kwon, Young Hye

doi:10.5487/tr.2013.29.1.007

Cited by 22 publications

(15 citation statements)

References 33 publications

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“…Liver dysfunction, attributable to liver damage associated with fatty liver, may be a part of the explanation for this phenomenon, insofar as the capacity of a damaged liver to pick up the extra TGs from the serum might be somewhat impaired. Additionally, low serum TGs have been associated with low betaine levels in mice [ 72 ], which was observed in the metabolomic analysis in our study (discussed in more detail in the following section). All these results are in agreement with previous observations that HCBD causes a metabolic stress response in blunt snout bream [ 31 ].…”

Section: Discussionsupporting

confidence: 69%

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Transcriptomics, metabolomics and histology indicate that high-carbohydrate diet negatively affects the liver health of blunt snout bream (Megalobrama amblycephala)

et al. 2017

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BackgroundGlobal trend of the introduction of high levels of relatively cheap carbohydrates to reduce the amount of costly protein in the aquatic animal feed production has affected the aquaculture of an economically important cyprinid fish, blunt snout bream (Megalobrama amblycephala). This dietary shift has resulted in increased prevalence of metabolic disorders, often causing economic losses. High dietary intake of carbohydrates, associated with obesity, is one of the major causes of non-alcoholic fatty liver disease (NAFLD) in humans.ResultsWe have conducted an eight-week feeding trial to better understand how a high-carbohydrate diet (HCBD) affects the liver health in this fish. Hepatosomatic index and lipid content were significantly (P < 0.05) higher in the HCBD group. Histology results also suggested pathological changes in the livers of HCBD group, with excessive lipid accumulation and indication of liver damage. Metabolomics and serum biochemistry analyses showed that a number of metabolites indicative of liver damage were increased in the HCBD group. This group also exhibited low levels of betaine, which is a metabolite crucial for maintaining the healthy liver functions. Transcriptomic and qPCR analyses indicated that HCBD had a strong impact on the expression of a large number of genes associated with the NAFLD and insulin signalling pathways, which may lead to the development of insulin resistance in hepatocytes, pathological liver changes, and eventually the NAFLD.ConclusionsTranscriptomics, metabolomics and histology results all indicate early symptoms of liver damage. However whether these would actually lead to the development of NAFLD after a longer period of time, remains inconclusive. Additionally, a very high number of upregulated genes in the HCBD group associated with several neurodegenerative diseases is a strong indication of neurodegenerative changes caused by the high-carbohydrate diet in blunt snout bream. This suggests that fish might present a good model to study neurodegenerative changes associated with high-carbohydrate diet in humans.Electronic supplementary materialThe online version of this article (10.1186/s12864-017-4246-9) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 69%

“…It is known that a decline in betaine is correlated with lower serum TGs in a diabetic mouse model [ 72 ]. Therefore, lower serum TG levels in the HCBD group are also consistent with the liver metabolomics results, where betaine was significantly reduced in the HCBD group.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomics, metabolomics and histology indicate that high-carbohydrate diet negatively affects the liver health of blunt snout bream (Megalobrama amblycephala)

et al. 2017

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“…As an osmolyte, betaine increases the water retention of cells, replaces inorganic salts, and protects against osmotic shocks [35]. Betaine has been used with good results in a variety of experimental disease models, including AGA, alcohol liver disease, nonalcoholic fatty liver disease, obesity, diabetes and multiple sclerosis [15,24,25,[36][37][38][39][40][41][42][43][44]. Although its mechanism of action is not fully understood, it is suggested to act primarily as methyl donor in several metabolic reactions, or to influence epigenetic marks.…”

Section: Discussionmentioning

confidence: 99%

Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I

Mosca

Vlekkert

Campos

et al. 2020

JCM

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Congenital deficiency of the lysosomal sialidase neuraminidase 1 (NEU1) causes the lysosomal storage disease, sialidosis, characterized by impaired processing/degradation of sialo-glycoproteins and sialo-oligosaccharides, and accumulation of sialylated metabolites in tissues and body fluids. Sialidosis is considered an ultra-rare clinical condition and falls into the category of the so-called orphan diseases, for which no therapy is currently available. In this study we aimed to identify potential therapeutic modalities, targeting primarily patients affected by type I sialidosis, the attenuated form of the disease. We tested the beneficial effects of a recombinant protective protein/cathepsin A (PPCA), the natural chaperone of NEU1, as well as pharmacological and dietary compounds on the residual activity of mutant NEU1 in a cohort of patients’ primary fibroblasts. We observed a small, but consistent increase in NEU1 activity, following administration of all therapeutic agents in most of the fibroblasts tested. Interestingly, dietary supplementation of betaine, a natural amino acid derivative, in mouse models with residual NEU1 activity mimicking type I sialidosis, increased the levels of mutant NEU1 and resolved the oligosacchariduria. Overall these findings suggest that carefully balanced, unconventional dietary compounds in combination with conventional therapeutic approaches may prove to be beneficial for the treatment of sialidosis type I.

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“…It had been reported that a decline in betaine indicates lower serum TG in the diabetic db/db mouse model [30]. Betaine is the product of the irreversible oxidation of choline in the liver and kidney.…”

Section: Discussionmentioning

confidence: 99%

“…Insulin resistance accompanied this accumulation of hepatic glycogen [29][30][31][32] and insulin resistance is one cause of fatty liver disease.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic and Metabolomics Analyses Show that High Carbohydrate Induces Fatty Liver in Blunt Snout Bream (<em>Megalobrama amblycephala</em>)<strong></strong>

Prisingkorn

Prathomya

Liu

et al. 2017

Preprint

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A high intake of carbohydrates, associated with obesity, is one of the major causes of fatty liver disease in humans.This study investigated how high carbohydrate intake induces fatty liver disease in Blunt snout bream (Megalobrama amblycephala). Blunt snout bream were fed a high-carbohydrate diet (HCBD) for 60 days. Their growth indices were evaluated, and the transcriptomes, metabolites, biochemistry, and histology of their blood and livers were analyzed. The final weight, weight gain, specific growth rate, and feed conversion ratio were all higher in the HCBD group than in the control group, but not significantly so (P > 0.05). The hepatosomatic index (HSI) differed significantly in the two groups (P < 0.05), and the metabolomics results showed that a high carbohydrate intake induced significant increases in plasma α/β-glucose, succinate, and tyrosine, which could increase hepatic glycogen and triglyceride. Low levels of betaine were also found in the livers of the HCBD group. The histology and blood biochemistry results suggested abnormal liver, with excessive lipid accumulation and liver damage. A transcriptome analysis and quantitative reverse transcription-PCR (RT-qPCR) indicated that the expression of the factors INSR, IRS, PI3K, PDK, AKT, ACC, IL6, AP1, ChREBP-MLX, PEPCK, and FBP in the insulin signaling pathway was significantly upregulated and that of SOCS3, GSK3β, and AMPK significantly downregulated in the HCBD. This pattern is associated with the nonalcoholic fatty liver disease (NAFLD) pathway. This study extends our understanding of how high carbohydrate causes increased fat deposition in the liver, enhanced glycolysis (α/β-glucose) in the plasma, and reduced betaine in the liver. This leads to activation of hepatocyte insulin resistance and lipogenesis by regulating the expression of genes related to fatty liver disease.Keyword: blunt snout bream; high carbohydrate; transcriptome; metabolomics; insulin resistance; fatty liver disease Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted:

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Betaine Alleviates Hypertriglycemia and Tau Hyperphosphorylation in db/db Mice

Cited by 22 publications

References 33 publications

Transcriptomics, metabolomics and histology indicate that high-carbohydrate diet negatively affects the liver health of blunt snout bream (Megalobrama amblycephala)

Transcriptomics, metabolomics and histology indicate that high-carbohydrate diet negatively affects the liver health of blunt snout bream (Megalobrama amblycephala)

Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I

Transcriptomic and Metabolomics Analyses Show that High Carbohydrate Induces Fatty Liver in Blunt Snout Bream (<em>Megalobrama amblycephala</em>)<strong></strong>

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