Energy restriction in obese subjects impact differently two mitochondrial function markers

Abstract

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.

The biochemistry of ketogenesis and its role in weight management, neurological disease and oxidative stress

“…A role for ketone bodies in improving mitochondrial function and reducing systemic oxidative stress has been identified [7], and a state of ketosis has also been shown to be favorable in Alzheimer's disease, ostensibly through a similar mechanism [49]. The pathophysiology of Alzheimer's disease involves the formation and deposition of β-amyloid, which may be initiated by an inappropriate inflammatory response.…”

“…In extra hepatic tissues, ketone bodies are activated by acetoacetate: succinyl CoA CoA transferase and converted to acetyl-CoA by β-ketothiolase (5), which permits their passage into the TCA cycle. α-Ketoglutarate can be funneled towards glutamate synthesis either directly via glutamate dehydrogenase (6) or by transamination (7). The glutamate so-formed may be used for GABA synthesis, or be converted to the tripeptide glutathione; however, this latter process is heavily dependent on cysteine availability…”

Beneficial Effects of the RESMENA Dietary Pattern on Oxidative Stress in Patients Suffering from Metabolic Syndrome with Hyperglycemia Are Associated to Dietary TAC and Fruit Consumption

“…Moreover, energy-restricted dietary strategies have demonstrated to be able to decrease MDA levels [44]. At the end of the study, both dietary treatments had reduced these biomarker levels; the control group showed statistically significant changes ( p = 0.007), and the RESMENA group showed a trend towards significance ( p = 0.079).…”

Lymphocytes Mitochondrial Physiology as Biomarker of Energy Metabolism during Fasted and Fed Conditions

“…On this way, OXPHOS is presented as a differentiated marker of insulin secretion concentration and capacity [16]. In another work, obese subjects submitted to hypocaloric diets demonstrated, after 8 weeks, reduction of inflammatory and oxidative stress markers and also of leptin levels, and an increase in leukocytes ATP contents [17]. …”