Assessment of human liver metabolism by phosphorus-31 magnetic resonance spectroscopy

Oberhaensli, Rolf D.; Galloway, Graham J.; Taylor, Doris J.; Bore, Peter J.; Radda, George K.

doi:10.1259/0007-1285-59-703-695

Cited by 98 publications

(36 citation statements)

References 9 publications

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“…Another follow-up study indicated that both surplus calories and excessive sucrose consumption play a role in the rise of liver enzyme levels (23). Additional evidence that fructose can cause steatohepatitis is that intravenous administration of fructose to healthy volunteers has resulted in a 75% decrease in hepatic ATP within 10 min because the liver was overwhelmed and could not metabolize it (24). Fructose can also increase triglyceride levels, de novo synthesis of fatty acids, hyperuricemia and insulin resistance (25).…”

Section: Discussionmentioning

confidence: 99%

Soft Drink Consumption Linked with Fatty Liver in the Absence of Traditional Risk Factors

Assy

Nasser

Kamayse

et al. 2008

Canadian Journal of Gastroenterology

291

194

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BACKGROUND: Little is known about dietary habits and their relationships with liver disease in nonalcoholic fatty liver disease (NAFLD) patients, particularly in the absence of obesity, diabetes or hyperlipidemia. OBJECTIVE: To assess the association between soft drink consumption and the presence of fatty liver in NAFLD patients who do not have classic risk factors. METHODS: Three hundred ten patients with NAFLD diagnosed by ultrasound were assessed for 36 months in a cross-sectional manner. Thirty-one patients (10%) who had NAFLD without classic risk factors were compared with 30 healthy controls. Physical activity was assessed during the preceding week and year, and every six months for 36 months. Data on daily dietary intake of food and soft drink, and the source of added sugar were collected during two seven-day periods, at the beginning of the study, and within two weeks after the metabolic tests by using a validated food questionnaire given by a trained dietician. Insulin resistance and lipid peroxidation were assessed by homeostasis model assessment-insulin resistance index (HOMA-IRI) and malondialdehyde (MDA) levels, respectively. RESULTS: Eighty per cent of patients (25 of 31) consumed an excessive amount of soft drink beverages (more than 50 g/day of added sugar) for 36 months, compared with 20% in healthy controls (P<0.001). Twenty per cent of patients consumed one drink per day, 40% consumed two to three drinks per day, and 40% consumed more than four drinks per day for most days during 36 months. The most common soft drinks consumed were regular Coca-Cola (40% of patients), Diet Coke (40%) and flavoured fruit juices (20%). Ultrasound findings revealed mild fatty liver in 44% of cases (n=14), moderate fatty liver in 38% (n=12), and severe fatty liver in 18% (n=5). HOMA-IRI and MDA levels were significantly higher in patients with NAFLD than in healthy controls (HOMA-IRI, 3.7 versus 1.7, P<0.001; and MDA, 420±300 μmol/mL versus 200±100 μmol/mL; P<0.001). When controlled for other factors, including dietary composition and physical activity, soft drink beverage consumption was the only independent variable that was able to predict the presence of fatty liver in 82.5% of cases with a sensitivity of 100%, a specificity of 76%, a positive predictive value of 57% and a negative predictive value of 100%. CONCLUSION: The present study may add important insight into the role of sugar-sweetened beverage consumption as a cause of fatty liver in patients without risk factors. Patients are encouraged to change their long-standing drinking behaviour.

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Section: Discussionmentioning

confidence: 99%

Soft Drink Consumption Linked with Fatty Liver in the Absence of Traditional Risk Factors

Assy

Nasser

Kamayse

et al. 2008

Canadian Journal of Gastroenterology

291

194

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“…Levels of intracellular free Mg 2ϩ and Mg-ATP have been determined with P-31 MRS in a variety of human tissues, including red blood cells, brain, liver, and muscle (14,(16)(17)(18). Magnesium deficiency has been reported in involved tissues in a number of clinical conditions, including hypertension, arteriosclerosis, cardiac arrhythmias, diabetes mellitus, and eosinophilia-myalgia syndrome (19)(20)(21).…”

Section: Conclusion Low Levels Of Mg-atp and Free Mgmentioning

confidence: 99%

Magnesium abnormalities of skeletal muscle in dermatomyositis and juvenile dermatomyositis

Niermann

Olsen

Park

2002

Arthritis & Rheumatism

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Objective. To characterize abnormalities in magnesium levels in the muscles of patients with dermatomyositis (DM) and juvenile dermatomyositis (JDM) and to evaluate the beneficial effects of prednisone and immunosuppressive therapy in elevating free magnesium (Mg 2؉ ) and ATP-bound magnesium (Mg-ATP).Methods. The study groups consisted of 12 adult patients with DM and 10 juvenile patients with JDM. The 2 control groups were 11 normal adults and 6 healthy children. Levels of total ATP in the quadriceps muscles of the subjects were determined during rest, exercise, and recovery, using noninvasive P-31 magnetic resonance spectroscopy (MRS). Concentrations of the biologically active free Mg 2؉ and the enzymatically active Mg-ATP complex were determined from the spectroscopy data by calculation of the chemical shifts of the ␤-phosphate peak of ATP.Results. Mg-ATP levels in DM and JDM myopathic muscles were at least 37% lower than those in normal muscles during rest, exercise, and recovery from exercise (P < 0.0005). Free Mg 2؉ levels were normal in DM and JDM myopathic muscles at rest, but were significantly lower than control values during exercise and recovery (P < 0.029 and P < 0.005 for DM and JDM, respectively). Prednisone and immunosuppressive therapy partially reversed the magnesium abnormalities, as evidenced by elevation of the levels of Mg-ATP and free Mg 2؉ .Conclusion. Low levels of Mg-ATP and free Mg 2؉ are concordant with weakness and fatigue observed in DM and JDM patients. Immunosuppressive therapy alleviates, in part, the magnesium deficits in the diseased muscles. Therefore, Mg-ATP and free Mg 2؉ may play a significant role in the pathophysiology of these diseases.Dermatomyositis (DM) and juvenile dermatomyositis (JDM) are similar yet distinct autoimmune diseases characterized by an erythematous rash and severe proximal muscle weakness. The classic diagnoses of DM and JDM are based on the findings of clinical evaluation, elevated serum levels of muscle enzymes, abnormal electromyographic results, and muscle inflammation on biopsy. More recently, magnetic resonance imaging (MRI) and P-31 magnetic resonance spectroscopy (MRS) have been employed as noninvasive techniques for the evaluation of patients with adult and juvenile DM (1-5).MRI has proven to be a reliable indicator of the extent and severity of muscle inflammation. P-31 MRS monitors metabolic status by determining the levels of the high-energy phosphate compounds ATP and phosphocreatine (PCr), which are required for muscle contraction. These compounds are greatly reduced in the affected muscles of patients with DM and JDM (1,4-6). During exercise and recovery, these patients demonstrate inefficient utilization and regeneration of ATP and PCr (1,5,6). Since MRI and MRS are noninvasive procedures with no known side effects, these techniques may be used to quantitatively evaluate the patients' responses to therapy on a longitudinal basis (7).In the present study, we used P-31 MRS to investigate the abnormalities in magnesium levels in the diseas...

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“…7,8 This was demonstrated in humans, in whom the intravenous administration of fructose (250 mg per kg of body weight over 5 min) resulted in a 75% reduction in hepatic ATP concentration. 8 In addition, fructose administration to rats was reported to reduce plasma inorganic phosphate (Pi), hepatic Pi and ATP, whereas previous phosphate loading attenuated the reductions of ATP and Pi, and a strong correlation was found between hepatic Pi and ATP. 9 Moreover, insulin release following glucose ingestion is known to increase extrahepatic phosphorus uptake, which would compromise hepatic phosphorus availability.…”

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confidence: 96%

“…6 Fructose is known to have 'phosphatesequestering' capacity, by virtue of which the phosphate attaches covalently to organic molecules, rendering it unavailable to participate in other essential metabolic reactions, including the regeneration of ATP. 7,8 This was demonstrated in humans, in whom the intravenous administration of fructose (250 mg per kg of body weight over 5 min) resulted in a 75% reduction in hepatic ATP concentration. 8 In addition, fructose administration to rats was reported to reduce plasma inorganic phosphate (Pi), hepatic Pi and ATP, whereas previous phosphate loading attenuated the reductions of ATP and Pi, and a strong correlation was found between hepatic Pi and ATP.…”

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confidence: 96%

Increased phosphorus content of preload suppresses ad libitum energy intake at subsequent meal

2010

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LebanonFood intake is believed to be partially controlled by hepatic signals related to adenosine triphosphate (ATP) status. We hypothesized that increased phosphorus content of one meal can stimulate hepatic ATP synthesis of the next meal, which in turn contributes to satiation. This hypothesis was tested by measuring the energy intake after phosphorus addition to several preloads. The phosphorus content of the different preloads was found to be inversely related to the energy intake at a subsequent meal, although the exact mechanism behind such effects was not studied. Such findings point to a potential role for phosphorus in the control of food intake. In humans, food intake is known to be controlled by both physiological and non-physiological factors, in which the former are believed to be partially governed by signals originating from the liver. 1,2 There is accumulating evidence of a negative relationship between hepatic ATP level and eating behavior; the changes in hepatic ATP (energy status) is thought to be transduced into neural or hepatic vagal afferent activity, which is transmitted to the central nervous system and which eventually controls food intake. 1,2 This relationship is based on data from several studies, in which the administration of a fructose analog, 2,5-anhydro-D-mannitol (2,5-AM), which causes a decline in the amount of inorganic phosphate necessary for ATP synthesis in the liver 3 ; or L-ethionine (which traps adenine and thus lowers ATP production) 4 to rats was found to stimulate eating behavior. Moreover, the hepatic ratio of ATP to ADP (adenosine diphosphate) (or the phosphorylation potential of the cell) was reported to be a more sensitive index of cellular energy status than ATP content. 5 This relationship implies that an increase in postprandial hepatic ATP synthesis triggers satiation, and the faster that the hepatic ATP increases, the greater the reduction in energy intake. In the postprandial state, phosphorus is utilized for the phosphorylation of many metabolites and its uptake by extrahepatic tissue is stimulated by insulin release, and thus its availability for hepatic ATP production may be compromised. Therefore, it is reasonable to postulate that the provision of a surplus amount of phosphorus in one meal would improve the hepatic phosphorus status or would offset any reduction caused by the second meal. This in turn would accelerate hepatic ATP synthesis, leading to an early termination of the eating episode.Increased consumption of fructose, mainly in the form of high-fructose corn syrup, has paralleled the rise in obesity and this has raised a concern over fructose's involvement in weight gain. 6 Fructose is known to have 'phosphatesequestering' capacity, by virtue of which the phosphate attaches covalently to organic molecules, rendering it unavailable to participate in other essential metabolic reactions, including the regeneration of ATP. 7,8 This was demonstrated in humans, in whom the intravenous administration of fructose (250 mg per kg of body weight over 5 ...

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Assessment of human liver metabolism by phosphorus-31 magnetic resonance spectroscopy

Cited by 98 publications

References 9 publications

Soft Drink Consumption Linked with Fatty Liver in the Absence of Traditional Risk Factors

Soft Drink Consumption Linked with Fatty Liver in the Absence of Traditional Risk Factors

Magnesium abnormalities of skeletal muscle in dermatomyositis and juvenile dermatomyositis

Increased phosphorus content of preload suppresses ad libitum energy intake at subsequent meal

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