Biotin deprivation impairs mitochondrial structure and function and has implications for inherited metabolic disorders

Ochoa-Ruiz, Estefanía; Díaz-Ruiz, Rodrigo; Hernández-Vázquez, Alain; Ibarra-González, Isabel; Ortíz-Plata, Alma; Rembao, Daniel; Ortega-Cuéllar, Daniel; Viollet, Benoı̂t; Uribe‐Carvajal, Salvador; Corella, José Ahmed; Velázquez-Arellano, Antonio

doi:10.1016/j.ymgme.2015.08.009

Cited by 15 publications

(14 citation statements)

References 48 publications

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“…Here we describe several of these in mice and in their livers. Interestingly, our findings on ThDEF are comparable to several of our previous results on the deficiency of another vitamin, biotin [6][7][8] .…”

Section: Introductionsupporting

confidence: 91%

“…It is well known that glucose can be completely oxidized without the participation of biotin, but not thiamine. The reduced hepatic ATP levels and the consequent AMPK activation are most likely due to the parallel functions as prosthetic groups -thiamine of pyruvate dehydrogenase and biotin of pyruvate carboxylase -being indispensable cofactors for the reduction of NADH and FADH 2 , which are sources of electrons for the oxidative generation of ATP [6] .…”

Section: Discussionmentioning

confidence: 99%

“…Energy Status: Adenine Nucleotides ATP, ADP, and AMP levels were determined by HPLC [6] . Mice were sacrificed, and a portion of hepatic tissue was immediately removed (0.8-1 g) and immersed in 3 mL of perchloric acid 8%, homogenized, and centrifuged (10,000 rpm for 10 min at 4 ° C).…”

Section: Thiamine Pyrophosphate Hplc Assaymentioning

confidence: 99%

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Thiamine Deprivation Produces a Liver ATP Deficit and Metabolic and Genomic Effects in Mice: Findings Are Parallel to Those of Biotin Deficiency and Have Implications for Energy Disorders

et al. 2016

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Thiamine is one of several essential cofactors for ATP generation. Its deficiency, like in beriberi and in the Wernicke-Korsakoff syndrome, has been studied for many decades. However, its mechanism of action is still not completely understood at the cellular and molecular levels. Since it acts as a coenzyme for dehydrogenases of pyruvate, branched-chain keto acids, and ketoglutarate, its nutritional privation is partly a phenocopy of inborn errors of metabolism, among them maple syrup urine disease. In the present paper, we report metabolic and genomic findings in mice deprived of thiamine. They are similar to the ones we have previously found in biotin deficiency, another ATP generation cofactor. Here we show that thiamine deficiency substantially reduced the energy state in the liver and activated the energy sensor AMP-activated kinase. With this vitamin deficiency, several metabolic parameters changed: blood glucose was diminished and serum lactate was increased, but insulin, triglycerides, and cholesterol, as well as liver glycogen, were reduced. These results indicate a severe change in the energy status of the whole organism. Our findings were associated with modified hepatic levels of the mRNAs of several carbon metabolism genes: a reduction of transcripts for liver glucokinase and fatty acid synthase and augmentation of those for carnitine palmitoyl transferase 1 and phosphoenolpyruvate carboxykinase as markers for glycolysis, fatty acid synthesis, beta-oxidation, and gluconeogenesis, respectively. Glucose tolerance was initially increased, suggesting augmented insulin sensitivity, as we had found in biotin deficiency; however, in the case of thiamine, it was diminished from the 3rd week on, when the deficient animals became undernourished, and paralleled the changes in AKT and mTOR, 2 main proteins in the insulin signaling pathway. Since many of the metabolic and gene expression effects on mice deprived of thiamine are similar to those in biotin deficiency, it may be that they result from a more general impairment of oxidative phosphorylation due to a shortage of ATP generation cofactors. These findings may be relevant to energy-related disorders, among them several inborn errors of metabolism, as well as common energy disorders like obesity, diabetes, and neurodegenerative illnesses.

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Section: Introductionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Thiamine Deprivation Produces a Liver ATP Deficit and Metabolic and Genomic Effects in Mice: Findings Are Parallel to Those of Biotin Deficiency and Have Implications for Energy Disorders

et al. 2016

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“…Growth retardation and malfunction of reproductive organs and ovulation; congenital debility of young animals with loss of both equilibrium and coordination [109,110] Zinc Reduced immune responses after challenging with pathogen indicated by greater weight loss, stool shedding, mucus production and diarrhea [111] Iodine Development of carcinoma of the thyroid; formation of oxidative stress and DNA modifications [112,113] Selenium Potentiate the development of autoantibodies; reduction of amino acid levels and elevation of mononucleotides resulting in dysregulated metabolomes and age-associated decline of protein synthesis; development of widespread pyogranulomas [114][115][116] Thiamine Reduction of energy state in the liver; reduction of blood glucose, insulin, triglycerides, cholesterol, liver glycogen; increase of serum lactate [117] Biotin Impairment of mitochondrial structure and function; intoxication with propionyl-CoA; systemic inflammation [118] Vitamin D…”

Section: Manganesementioning

confidence: 99%

All You Can Feed: Some Comments on Production of Mouse Diets Used in Biomedical Research with Special Emphasis on Non-Alcoholic Fatty Liver Disease Research

et al. 2020

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The laboratory mouse is the most common used mammalian research model in biomedical research. Usually these animals are maintained in germ-free, gnotobiotic, or specific-pathogen-free facilities. In these facilities, skilled staff takes care of the animals and scientists usually don’t pay much attention about the formulation and quality of diets the animals receive during normal breeding and keeping. However, mice have specific nutritional requirements that must be met to guarantee their potential to grow, reproduce and to respond to pathogens or diverse environmental stress situations evoked by handling and experimental interventions. Nowadays, mouse diets for research purposes are commercially manufactured in an industrial process, in which the safety of food products is addressed through the analysis and control of all biological and chemical materials used for the different diet formulations. Similar to human food, mouse diets must be prepared under good sanitary conditions and truthfully labeled to provide information of all ingredients. This is mandatory to guarantee reproducibility of animal studies. In this review, we summarize some information on mice research diets and general aspects of mouse nutrition including nutrient requirements of mice, leading manufacturers of diets, origin of nutrient compounds, and processing of feedstuffs for mice including dietary coloring, autoclaving and irradiation. Furthermore, we provide some critical views on the potential pitfalls that might result from faulty comparisons of grain-based diets with purified diets in the research data production resulting from confounding nutritional factors.

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“…Four out of the five carboxylases are located in the mitochondria, and accordingly, biotin deficiencies result in abnormal mitochondrial structures and functions. 2 Biotin is taken up by the cells via a sodium-dependent vitamin transporter (SMVT), expressed in the cytoplasm and the mitochondrial membranes. SMVT is present in the gastrointestinal tract, liver, kidneys, retina, heart, brain, and skin.…”

Section: Introductionmentioning

confidence: 99%

Imaging Biotin Trafficking In Vivo with Positron Emission Tomography

et al. 2020

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The water-soluble vitamin biotin is essential for cellular growth, development, and well-being, but its absorption, distribution, metabolism, and excretion are poorly understood. This paper describes the radiolabeling of biotin with the positron emission tomography (PET) radionuclide carbon-11 ([ 11 C]biotin) to enable the quantitative study of biotin trafficking in vivo. We show that intravenously administered [ 11 C]biotin is quickly distributed to the liver, kidneys, retina, heart, and brain in rodents—consistent with the known expression of the biotin transporter—and there is a surprising accumulation in the brown adipose tissue (BAT). Orally administered [ 11 C]biotin was rapidly absorbed in the small intestine and swiftly distributed to the same organs. Preadministration of nonradioactive biotin inhibited organ uptake and increased excretion. [ 11 C]Biotin PET imaging therefore provides a dynamic in vivo map of transporter-mediated biotin trafficking in healthy rodents. This technique will enable the exploration of biotin trafficking in humans and its use as a research tool for diagnostic imaging of obesity/diabetes, bacterial infection, and cancer.

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Biotin deprivation impairs mitochondrial structure and function and has implications for inherited metabolic disorders

Cited by 15 publications

References 48 publications

Thiamine Deprivation Produces a Liver ATP Deficit and Metabolic and Genomic Effects in Mice: Findings Are Parallel to Those of Biotin Deficiency and Have Implications for Energy Disorders

Thiamine Deprivation Produces a Liver ATP Deficit and Metabolic and Genomic Effects in Mice: Findings Are Parallel to Those of Biotin Deficiency and Have Implications for Energy Disorders

All You Can Feed: Some Comments on Production of Mouse Diets Used in Biomedical Research with Special Emphasis on Non-Alcoholic Fatty Liver Disease Research

Imaging Biotin Trafficking In Vivo with Positron Emission Tomography

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