Impact of GLP-1 receptor agonist versus omega-3 fatty acids supplement on obesity-induced alterations of mitochondrial respiration.

Objective: To compare administration of the glucagon-like peptide-1 (GLP-1) analogue, exenatide, versus dietary supplementation with the omega-3 fatty acid-rich Calanus oil on obesity-induced alterations in mitochondrial respiration. Methods: Six-week-old female C57BL/6JOlaHSD mice were given high fat diet (HFD, 45% energy from fat) for 12 weeks to induce obesity. Thereafter, they were divided in three groups where one received exenatide (10 µg/kg/day) via subcutaneously implanted mini-osmotic pumps, a second group received 2% Calanus oil as dietary supplement, while the third group received HFD without any treatment. Animals were sacrificed after 8 weeks of treatment and tissues (skeletal muscle, liver, and white adipose tissue) were collected for measurement of mitochondrial respiratory activity by high-resolution respirometry, using an Oroboros Oxygraph-2k (Oroboros instruments, Innsbruck, Austria). Results: It was found that high-fat feeding led to a marked reduction of mitochondrial respiration in adipose tissue during all three states investigated - LEAK, OXPHOS and ETS. This response was to some extent attenuated by exenatide treatment, but not with Calanus oil treatment. High-fat feeding had no major effect on hepatic mitochondrial respiration, but exenatide treatment resulted in a significant increase in the various respiratory states in liver. Mitochondrial respiration in skeletal muscle was not significantly influenced by high-fat diet or any of the treatments. The precise evaluation of mitochondrial respiration considering absolute oxygen flux and ratios to assess flux control efficiency avoided misinterpretation of the results. Conclusions: Exenatide increased hepatic mitochondrial respiration in high-fat fed mice, but no clear beneficial effect was observed in skeletal muscle or fat tissue. Calanus oil did not negatively affect respiratory activity in these tissues, which maintains its potential as a dietary supplement, due to its previously reported benefits on cardiac function.

Effects of Lifestyle Intervention in Tissue-Specific Lipidomic Profile of Formerly Obese Mice.

Lipids are highly diverse in their composition, properties and distribution in different biological entities. We aim to establish the lipidomes of several insulin-sensitive tissues and to test their plasticity when divergent feeding regimens and lifestyles are imposed. Here, we report a proton nuclear magnetic resonance (1H-NMR) study of lipid abundance across 4 tissues of C57Bl6J male mice that includes the changes in the lipid profile after every lifestyle intervention. Every tissue analysed presented a specific lipid profile irrespective of interventions. Glycerolipids and fatty acids were most abundant in epididymal white adipose tissue (eWAT) followed by liver, whereas sterol lipids and phosphoglycerolipids were highly enriched in hypothalamus, and gastrocnemius had the lowest content in all lipid species compared to the other tissues. Both when subjected to a high-fat diet (HFD) and after a subsequent lifestyle intervention (INT), the lipidome of hypothalamus showed no changes. Gastrocnemius and liver revealed a pattern of increase in content in many lipid species after HFD followed by a regression to basal levels after INT, while eWAT lipidome was affected mainly by the fat composition of the administered diets and not their caloric density. Thus, the present study demonstrates a unique lipidome for each tissue modulated by caloric intake and dietary composition.