In vivo assessment of the mitochondrial response to caloric restriction in obese women by the 2-keto[1-13C]isocaproate breath test

Parra, Dolores Aleixandre; González, Álvaro; Martínez, Jean; Labayen, Idoia; Díez, Nieves Lagares

doi:10.1053/meta.2003.50075

Cited by 18 publications

(35 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous reports, employing KICA and octanoate respectively as breath test substrates for mitochondrial function, also indicated a normal mitochondrial amino acid metabolism [39] or an even accelerated mitochondrial β-oxidation of medium-chain fatty acids [45] in patients with liver steatosis and in obese women without features of NASH [46].…”

Section: Discussionmentioning

confidence: 93%

Liver breath tests non-invasively predict higher stages of non-alcoholic steatohepatitis

et al. 2006

View full text Add to dashboard Cite

Effectively assessing subtle hepatic metabolic functions by novel non-invasive tests might be of clinical utility in scoring NAFLD (non-alcoholic fatty liver disease) and in identifying altered metabolic pathways. The present study was conducted on 39 (20 lean and 19 obese) hypertransaminasemic patients with histologically proven NAFLD {ranging from simple steatosis to severe steatohepatitis [NASH (non-alcoholic steatohepatitis)] and fibrosis} and 28 (20 lean and eight overweight) healthy controls, who underwent stable isotope breath testing ([(13)C]methacetin and [(13)C]ketoisocaproate) for microsomal and mitochondrial liver function in relation to histology, serum hyaluronate, as a marker of liver fibrosis, and body size. Compared with healthy subjects and patients with simple steatosis, NASH patients had enhanced methacetin demethylation (P=0.001), but decreased (P=0.001) and delayed (P=0.006) ketoisocaproate decarboxylation, which was inversely related (P=0.001) to the degree of histological fibrosis (r=-0.701), serum hyaluronate (r=-0.644) and body size (r=-0.485). Ketoisocaproate decarboxylation was impaired further in obese patients with NASH, but not in patients with simple steatosis and in overweight controls. NASH and insulin resistance were independently associated with an abnormal ketoisocaproate breath test (P=0.001). The cut-off value of 9.6% cumulative expired (13)CO(2) for ketoisocaproate at 60 min was associated with the highest prediction (positive predictive value, 0.90; negative predictive value, 0.73) for NASH, yielding an overall sensitivity of 68% and specificity of 94%. In conclusion, both microsomal and mitochondrial functions are disturbed in NASH. Therefore stable isotope breath tests may usefully contribute to a better and non-invasive characterization of patients with NAFLD.

show abstract

Section: Discussionmentioning

confidence: 93%

Liver breath tests non-invasively predict higher stages of non-alcoholic steatohepatitis

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Previous reports have shown a decrease in the tracer oxidation after an energy restriction treatment (1,23,24). The reason for the disparity with other studies may relate not only to the different nutritional treatment conditions, but also because the mitochondrial oxidation of KICA could be modulated by the type of nutritional intervention (1).…”

Section: Discussionmentioning

confidence: 93%

“…Therefore, the association between KICA-BT parameters with the adiposity and lipid metabolism could be related to the activation of alternative pathways in obese metabolism. Thus, the mitochondrial oxidation of KICA in obese subjects could be related to the lipid storage, showing a compensatory mechanism to increase the energy storage in conditions related to fuel economy as occurs in women (23). This energy saving mechanism could be downregulated after a hypocaloric diet treatment, which could improve mitochondrial oxidative capacity to the ATP synthesis by decreasing the proinflammatory and oxidative damage.…”

Section: Discussionmentioning

confidence: 97%

“…Also, the 2-keto [1-13 C]isocaproate breath test (KICA-BT) is a valid example for in vivo studying energy metabolism without biopsy sampling (25). This probe has been proposed as a tool to investigating the role that mitochondria may play in body weight management, since the pathway assessed by the breath test is closely related to energy homeostasis (23). Therefore, the aim of this study was focused to evaluate if it is possible to detect changes in the mitochondrial function in response to a balanced hypocaloric diet designed to lose weight in obese subjects by means of quantifying the ATP content in circulating leukocytes and by using the 2-keto [1-13 C]isocaproate breath test as well as to identifying possible relationships with inflammatory and oxidative stress circulating biomarkers, which appears to inhibit mitochondrial function and energy production in cells (29).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Energy restriction in obese subjects impact differently two mitochondrial function markers

Crujeiras

Parra

Goyenechea

et al. 2008

J. Physiol. Biochem.

View full text Add to dashboard Cite

Excessive fat deposition is the key feature in obesity, which is empowered by cytokines overproduction and stimulation of cell oxidative stress processes, but little is known about energy availability in the form of ATP and mitochondrial function in the obese subjects. Thus, the aim of this study was to evaluate the possible changes in energy metabolism after a 8-weeks balanced-hypocaloric diet in obese subjects by measuring the ATP-content in leukocytes, by assessing 2-keto[1-13C]isocaproate breath test (KICA-BT) parameters related to mitochondrial function and by analyzing inflammatory and oxidative stress biomarkers. All the recruited obese subjects (n = 19) lost body weight after dieting (-5.55 +/- 2.88%). The hypocaloric treatment induced a decrease in leptin levels and lipid peroxidation markers. Interestingly, the ATP content in blood leukocytes increased (49.9 +/- 32.5 vs 36.2 +/- 27.9 pmol/mg prot.; p < 0.05), while KICA tracer mitochondrial oxidation decreased (30.9 +/- 5.9 vs. 33.1 +/- 4.5 % 13C; p < 0.05) after weight loss. These results show that two minimally invasive methods were able to detect changes in mitochondrial function as induced by a hypocaloric diet, which is of great interest in order to understand oxidative processes associated with weight homeostasis as well as to establish newer anti-obesity therapeutic targets by using mitochondrial function markers in vivo.

show abstract

“…The breath test estimates mitochondrial oxidation from the decarboxylation of the 2-ketoisocaproate labelled with 13 C in the carboxylic acid group, measuring the exhalation of 13 CO 2 after the tracer ingestion (Parra et al 2003). Thus, breath samples were recovered by exhaling through a straw into a tube (Labco, High Wycombe, UK) before and at 10-min intervals during the 2 h after ingestion of the 2-keto[1-13 C]isocaproate.…”

Section: Mitochondrial Oxidation Measurementmentioning

confidence: 99%

Effects of two energy-restricted diets differing in the carbohydrate/protein ratio on weight loss and oxidative changes of obese men

Abete

Parra

Morentín

et al. 2009

International Journal of Food Sciences and Nutrition

Self Cite

View full text Add to dashboard Cite

show abstract

In vivo assessment of the mitochondrial response to caloric restriction in obese women by the 2-keto[1-13C]isocaproate breath test

Cited by 18 publications

References 21 publications

Liver breath tests non-invasively predict higher stages of non-alcoholic steatohepatitis

Liver breath tests non-invasively predict higher stages of non-alcoholic steatohepatitis

Energy restriction in obese subjects impact differently two mitochondrial function markers

Effects of two energy-restricted diets differing in the carbohydrate/protein ratio on weight loss and oxidative changes of obese men

Contact Info

Product

Resources

About