Comparative Metabolic Analysis of Lactate for CHO Cells in Glucose and Galactose

Camila A. Wilkens,Claudia Altamirano,Ziomara P. Gerdtzen 한국생물공학회 2011 Biotechnology and Bioprocess Engineering Vol.16 No.4

t-PA producing CHO cells have been shown to undergo a metabolic shift when the culture medium is supplemented with a mixture of glucose and galactose. This metabolic change is characterized by the reincorporation of lactate and its use as an additional carbon source. The aim of this work is to understand lactate metabolism. To do so,Chinese hamster ovary cells were grown in batch cultures in four different conditions consisting in different combinations of glucose and galactose. In experiments supplemented with glucose, only lactate production was observed. Cultures with glucose and galactose consumed glucose first and produced lactate at the same time, after glucose depletion galactose consumption began and lactate uptake was observed. Comparison of the metabolic state of cells with and without the shift by metabolic flux analysis show that the metabolic fluxes distribution changes mostly in the reactions involving pyruvate metabolism. When not enough pyruvate is being produced for cells to support their energy requirements, lactate dehydrogenase complex changes the direction of the reaction yielding pyruvate to feed the TCA cycle. The slow change from high fluxes during glucose consumption to low fluxes in galactose consumption generates intracellular conditions that allow the influx of lactate. Lactate consumption is possible in cell cultures supplemented with glucose and galactose due to the low rates at which galactose is consumed. Evidence suggests that an excessive production and accumulation of pyruvate during glucose consumption leads to lactate production and accumulation inside the cell. Other internal conditions such as a decrease in internal pH, forces the flow of lactate outside the cell. After metabolic shift the intracellular pool of pyruvate, lactate and H+ drops permitting the reversal of the monocarboxylate transporter direction, therefore leading to lactate uptake. Metabolic analysis comparing glucose and galactose consumption indicates that after metabolic shift not enough pyruvate is produced to supply energy metabolism and lactate is used for pyruvate synthesis. In addition, MFA indicates that most carbon consumed during low carbon flux is directed towards maintaining energy metabolism.

원저 : 호모시스테인과 대사증후군의 상관관계

신경필 ( Kyoung Pil Shin ),이상엽 ( Sang Yeoup Lee ),김윤진 ( Yun Jin Kim ),이정규 ( Jeong Gyu Lee ),김동희 ( Dong Hee Kim ),정동욱 ( Dong Wook Jung ),이유현 ( Yu Hyeon Yi ),박선기 ( Seon Ki Park ),조영혜 ( Young Hye Cho ) 대한비만학회 2011 The Korean journal of obesity Vol.20 No.1

연구배경: 대사증후군은 심혈관질환의 위험인자가 군집되어 나타나는 것으로 인슐린 저항성이 대사증후군의 주요한 병인으로 인식되고 있다. 호모시스테인은 methionine 대사과정에서 생성되는 아미노산으로 최근 인슐린 저항성과의 연관성이 보고되고 있다. 하지만 둘 사이의 직접적인 연관성에 관하여는 아직 논란의 여지가 많아, 본 연구에서 대사증후군과 호모시스테인 사이의 연관성을 살펴보고자 하였다. 방법: 2007년 1월 1일부터 2007년 12월 31일까지 일개 대학병원 건강증진센터를 방문한 수진자 중 20세 이상의 성인 4,488명을 최종 연구대상으로 하였다. 대사증후군의 진단기준은 modified ATPIII definition을 사용하였고, 그 중 허리둘레 기준은 한국인의 기준에 따랐다. 대사증후군 유무에 따른 호모시스테인 농도의 차이, 호모시스테인의 농도 차이에 따른 대사증후군 환자 비율을 조사하여, 대사증후군과 호모시스테인의 연관성을 보고자 하였다. 결과: 혈중 호모시스테인은 대사증후군을 가진 군이 대사증후군을 가지지 않은 군에 비하여 통계적으로 유의하게 높은 값을 보여주었다(9.10 vs 7.97, P < 0.001). 호모시스테인의 농도차이에 따른 대사증후군 유병률은 호모시스테인의 농도가 가장 낮은 4분위수와 비교하였을 때, 상위 4분위수 모두 교차비가 1.28, 1.48, 1.41로 유의하게 증가하는 것으로 나타났다(P < 0.05). 결론: 대사증후군과 호모시스테인은 통계적으로 유의한 연관성을 보이며, 이러한 기전을 확인하기 위한 전향적 연구가 필요하다. Background: Metabolic syndrome is a cluster of all the risk factors of cardiovascular diseases, in which insulin resistance plays a key role as the pathogenesis. Homocysteine is an amino acid that is generated during methionine metabolism. It is associated with insulin resistance. However, there is a controversy concerning the corelation between homocysteine and metabolic syndrome. This study is designed to further investigate this subject. Methods: A total of 4488 patients who were older than 20 years of age and visited the Health Promotion Center of a university affiliated hospital from Jan 1, 2007 to Dec 31, 2007 were assigned to this study. Modified ATP III definition was used for diagnosis of metabolic syndrome while Korean standard for waist circumference was used. This study tried to prove the correlation of homocysteine concentration and metabolic syndrome by using two statistical tools. The first was the comparison of homocysteine concentration between the group with and without metabolic syndrome. The second was the prevalence ratio of metabolic syndrome according to the level of homocysteine concentration. Results: The group with metabolic syndrome showed a significantly higher level of homocysteine compared to the other groups (9.10 vs 7.97, P < 0.001). In comparison to the group with the lowest (< 5.90 mg/L, Q1) homocysteine level, the prevalence of metabolic syndrome among the other groups (Q2.Q3 and Q4) were significantly higher with odds ratio being 1.28, 1.48 and 1.41 for groups Q2, Q3, and Q4, respectively. Conclusion: Metabolic syndrome was shown to have a significant correlation with a high level of homocysteine. Therefore, lowering homocysteine level may help prevent metabolic syndrome.

2세대 항정신병 약물의 대사증후군

이종범(Jong Bum Lee),서완석(Wan Seok Seo) 대한생물치료정신의학회 2007 생물치료정신의학 Vol.13 No.2

This study reviewed metabolic effects of second generation antipsychotics(SGAs). SGAs generally have greater risks for develping metabolic syndrome, such as weight gain, abnormality in glucose and lipid metabolism. Olanzapine and clozapine have greatest risks in weight gain and glucose metabolism abnormality. Meanwhile, aripiprazole and ziprasidone have least risks in developing metabolic syndrome. Various therapeutic approaches to reduce SGAs related metabolic syndrome were suggested. They are behavioral therapies and weight reduction medications, such as sibutramine, orlistat and topiramate. Careful monitoring of serum glucose, cholesterol level and weight gain are the most important things to prevent SGAs related metabolic syndrome. Future studies for developing SGAs related metabolic syndrome speicific therapeutic strategies and finding mechanisms of SGAs related metabolic abnormalies are needed.

비만에서 adipose tissue 호르몬에 의한 metabolic signaling

장영훈 한국생명과학회 2023 생명과학회지 Vol.33 No.3

Healthy adipose tissue is critical for preventing obesity by maintaining metabolic homeostasis. Adipose tissue plays an important role in energy homeostasis through glucose and lipid metabolism. Depending on nutritional status, adipose tissue expands to store lipids or can be consumed by lipolysis. The role of adipose tissue as an endocrine organ is emerging, and many studies have reported that there are various adipose tissue hormones that communicate with other organs and tissues through metabolic signaling. For example, leptin, a representative peptide hormone secreted from adipose tissues (adipokine), circulates and targets the central nervous system of the brain for appetite regression. Furthermore, adipocytes secrete inflammatory cytokines to target immune cells in adipose tissues. Not surprisingly, adipocytes can secrete fatty acid-derived hormones (lipokine) that bind to their specific receptors for paracrine and endocrine action. To understand organ crosstalk by adipose tissue hormones, specific metabolic signaling in adipocytes and other communicating cells should be defined. The dysfunction of metabolic signaling in adipocytes occurs in unhealthy adipose tissue in overweight and obese conditions. Therapy targeting novel adipose metabolic signaling could potentially lead to the development of an effective anti-obesity drug. This review summarizes the latest updates on adipose tissue hormone and metabolic signaling in terms of obesity and metabolic diseases.

중년여성의 신체활동 수준과 운동형태가 대사증후군 위험요인 및 에너지대사에 미치는 영향

이향범(Hyang Beum Lee) 한국발육발달학회 2014 한국발육발달학회지 Vol.22 No.4

The purpose of this study is to find out the effect of 8 weeks of participation in exercise by middleaged women on body composition, risk factors associated with metabolic syndrome and energy metabolism based on the level of physical activity and types of exercise and the effect on physical functions and provide basic information for effective exercise prescription. This study investigated the difference between factors depending on the level of physical activity by dividing groups into two; one is the active group with the physical activity of more than 1500METㆍmin/week and the other is the non-active group with less than 600METㆍmin/week of physical activity. The non-active group has again been divided into combined exercise group(n=9), the aerobic exercise group(n=9) and control group(n=9). The results of 8-weeks of participation in exercise depending on the type of exercise and its impact on risk factors associated with metabolic syndrome and energy metabolism are as follows. 1. As a result of the analysis of the difference of body composition, metabolic syndrome risk factors and energy metabolism using the Short-form on WHO International Physical Activity Questionnaires(IPAQ), there were the statistically significant differences for body composition in body fat percentage, for metabolic syndrome risk factors in neutral fats and HDL-Cholesterol and for energy metabolism in insulin and growth hormone. 2. As a result of the analysis of the difference of body composition according to the exercise types of non-active middle-aged women, there were the statistically significant differences for interaction effect in weight, BMI, body fat percentage and body fat amount and for exercising period in weight, body fat percentage and body fat amount. As a result of the analysis of the difference of metabolic syndrome risk factors, there were the statistically significant differences for interaction effect in blood sugar, neutral fats, HDL-C and waist measurement and for the exercising period in blood sugar, neutral fats, HDL-C and waist measurement. As a result of the analysis of the difference of energy metabolism, there were the statistically significant differences for interaction effect in free fatty acid, insulin, growth hormone and leptin and for the exercising period in free fatty acid, insulin, growth hormone and leptin. In case of exercising group, there were no statistically significant differences in body composition, metabolic syndrome risk factors and energy metabolism.

From nonalcoholic fatty liver disease to metabolic-associated fatty liver disease: Big wave or ripple?

( Seong Hee Kang ),( Yuri Cho ),( Soung Won Jeong ),( Seung Up Kim ),( Jin-woo Lee ) 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.2

There is some dissatisfaction with the term “nonalcoholic fatty liver disease (NAFLD),” which overemphasizes alcohol and underemphasizes the importance of metabolic risk factors in this disease. Recently, a consensus recommended “metabolic (dysfunction)-associated fatty liver disease (MAFLD)” as a more appropriate term to describe fatty liver diseases (FLD) associated with metabolic dysfunction. During the definition change from NAFLD to MAFLD, subjects with FLD and metabolic abnormalities, together with other etiologies of liver diseases such as alcohol, virus, or medication who have been excluded from the NAFLD criteria, were added to the MAFLD criteria, while subjects with FLD but without metabolic abnormality, who have been included in the NAFLD criteria, were excluded from the MAFLD criteria. This means that there is an emphasis on the metabolic dysfunction in MAFLD which may underestimate the prognostic value of hepatic steatosis itself, whereas the MAFLD criteria might better identify subjects who are at a higher risk of hepatic or cardiovascular outcomes. However, non-metabolic risk NAFLD subjects who are excluded from the MAFLD criteria are missed from the diagnosis, and their potential risk can be the cause of future diseases. Although huge controversies remain, this review focused on summarizing recent studies that compared the clinical and prognostic characteristics between subjects with NAFLD and MAFLD. (Clin Mol Hepatol 2021;27:257-269)

Model based engineering of <i>Pichia pastoris</i> central metabolism enhances recombinant protein production

Nocon, Justyna,Steiger, Matthias G.,Pfeffer, Martin,Sohn, Seung Bum,Kim, Tae Yong,Maurer, Michael,Rußmayer, Hannes,Pflü,gl, Stefan,Ask, Magnus,Haberhauer-Troyer, Christina,Ortmayr, Karin,Hann, Ste Academic Press 2014 Metabolic engineering Vol.24 No.-

<▼1><P>The production of recombinant proteins is frequently enhanced at the levels of transcription, codon usage, protein folding and secretion. Overproduction of heterologous proteins, however, also directly affects the primary metabolism of the producing cells. By incorporation of the production of a heterologous protein into a genome scale metabolic model of the yeast <I>Pichia pastoris</I>, the effects of overproduction were simulated and gene targets for deletion or overexpression for enhanced productivity were predicted. Overexpression targets were localized in the pentose phosphate pathway and the TCA cycle, while knockout targets were found in several branch points of glycolysis. Five out of 9 tested targets led to an enhanced production of cytosolic human superoxide dismutase (hSOD). Expression of bacterial β-glucuronidase could be enhanced as well by most of the same genetic modifications. Beneficial mutations were mainly related to reduction of the NADP/H pool and the deletion of fermentative pathways. Overexpression of the hSOD gene itself had a strong impact on intracellular fluxes, most of which changed in the same direction as predicted by the model. <I>In vivo</I> fluxes changed in the same direction as predicted to improve hSOD production. Genome scale metabolic modeling is shown to predict overexpression and deletion mutants which enhance recombinant protein production with high accuracy.</P></▼1><▼2><P><B>Highlights</B></P><P>•<P>Recombinant protein production in <I>P. pastoris</I> affects the central metabolism.</P>•<P>A genome scale metabolic model can predict these metabolic flux changes.</P>•<P>Mutations in central metabolic genes enhanced recombinant protein yield up to 40%.</P>•<P>These beneficial mutations were predicted by the metabolic model with high accuracy.</P></P></▼2>

Cognitive Impairments and Associated Structural Brain Changes in Metabolic Syndrome and Implications of Neurocognitive Intervention

Kordestani-Moghadam Parastou,Assari Shervin,Nouriyengejeh Sarah,Mohammadipour Fatemeh,Pourabbasi Ata 대한비만학회 2020 The Korean journal of obesity Vol.29 No.3

Currently, metabolic syndrome has become a global health problem. Alterations in neurocognitive functions among patients with metabolic syndrome are important issues in this disorder. In this paper, studies on metabolic syndrome were reviewed and their importance emphasized for the benefit of experts and policy makers. Metabolic syndrome activates inflammatory mediators that disrupt brain metabolism. These mediators can be activated by metabolic inflammation and microvascular disorders and may further cause damage to the white matter and impair cognitive function. These alterations can result in serious changes in cognitive abilities. The association between cognitive changes and metabolic syndrome has been independently evaluated in several studies. In addition, some areas of research in the field of metabolic syndrome include the effectiveness of neurocognitive interventions to enhance normal behaviors or reduce risky behaviors in patients. Structural brain correlates of health-related behaviors provide a basis for designing more effective behavioral interventions by identifying the corresponding brain regions and using behavioral interventions.

Revisiting the Bacterial Phylum Composition in Metabolic Diseases Focused on Host Energy Metabolism

이연미,이희영 대한당뇨병학회 2020 Diabetes and Metabolism Journal Vol.44 No.5

Over a hundred billion bacteria are found in human intestines. This has emerged as an environmental factor in metabolic diseases, such as obesity and related diseases. The majority of these bacteria belong to two dominant phyla, Bacteroidetes and Firmicutes. Since the ratio of Firmicutes to Bacteroidetes increases in people with obesity and in various animal models, it has been assumed that phylum composition causes the increase in occurrence of metabolic diseases over the past decade. However, this assumption has been challenged by recent studies that have found even an opposite association of phylum composition within metabolic diseases. Moreover, the gut microbiota affects host energy metabolism in various ways including production of metabolites and interaction with host intestinal cells to regulate signaling pathways that affect energy metabolism. However, the direct effect of gut bacteria on host energy intake, such as energy consumption by the bacteria itself and its effects on intestinal energy absorption, has been underestimated. This review aims to discuss whether increased ratio of Firmicutes to Bacteroidetes is associated with the development of metabolic diseases, and whether energy competition between the bacteria and host is a missing part of the mechanism linking gut microbiota to metabolic diseases.

건선에 효과적인 한약 처방 탐색 - 지질 대사를 중심으로

한창이,김준동,서광일,김규석,김윤범,Han, Chang-Yi,Kim, Jundong,Seo, Gwang-Yeel,Kim, Kyu-Seok,Kim, Yoon-Bum 대한한방안이비인후피부과학회 2021 한방안이비인후피부과학회지 Vol.34 No.3

Objectives : The purpose of this study is to investigate the possibility of using herbal medicine for the management of psoriasis focusing on lipid metabolism. Methods : We reviewed studies about pathophysiology, and medical treatment of psoriasis, the relationship between psoriasis and metabolic syndrome and lipid metabolism, and herbal medicine on Pubmed and Google scholar. Results : Psoriasis is a chronic multi-organ inflammatory disease not limited to skin, and steroids, immuno-suppressants, and biological agents are used. It is known that psoriasis and metabolic syndrome act as mutual risk factors, and lipid metabolism are involved in psoriasis. The effects of various single herbal preparations and complex herbal extract, decoction on improving lipid metabolism have been consistently reported, and there was an improvement of psoriatic skin lesions and improvement of blood lipid levels through herbal medicine. Conclusions : Herbal medicine research in psoriasis has focused on the anti-inflammatory effect and the suppression effect of certain immune mediators. However, considering that psoriasis is affected by lipid metabolism and side effects of Western medicines, the use of herbal medicines for the purpose of controlling lipid metabolism in psoriasis is useful in aspects of reducing side effects of concurrent Western medicine, improving the severity of psoriasis, and managing metabolic risk factors.