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.

Obesity-induced alterations in the gut microbiome in female mice fed a high-fat diet are antagonized by dietary supplementation with a novel, wax ester-rich, marine oil.

Dietary supplementation with calanus oil, a novel wax ester-rich marine oil, has been shown to reduce adiposity in high-fat diet (HFD)-induced obese mice. Current evidence suggests that obesity and its comorbidities are intrinsically linked with unfavorable changes in the intestinal microbiome. Thus, in line with its antiobesity effect, we hypothesized that dietary supplementation with calanus oil should counteract the obesity-related deleterious changes in the gut microbiota. Seven-week-old female C57bl/6J mice received an HFD for 12 weeks to induce obesity followed by 8-week supplementation with 2% calanus oil. For comparative reasons, another group of mice was treated with exenatide, an antiobesogenic glucagon-like peptide-1 receptor agonist. Mice fed normal chow diet or nonsupplemented HFD for 20 weeks served as lean and obese controls, respectively. 16S rRNA gene sequencing was performed on fecal samples from the colon. HFD increased the abundance of the Lactococcus and Leuconostoc genera relative to normal chow diet, whereas abundances of Allobaculum and Oscillospira were decreased. Supplementation with calanus oil led to an apparent overrepresentation of Lactobacillus and Streptococcus and underrepresentation of Bilophila. Exenatide prevented the HFD-induced increase in Lactococcus and caused a decrease in the abundance of Streptococcus compared to the HFD group. Thus, HFD altered the gut microbiota composition in an unhealthy direction by increasing the abundance of proinflammatory genera while reducing those considered health-promoting. These obesity-induced changes were antagonized by both calanus oil and exenatide.

Seasonal changes in background levels of deuterium and oxygen-18 prove water drinking by harp seals, which affects the use of the doubly labelled water method.

The aim of this study was to monitor seasonal changes in stable isotopes of pool freshwater and harp seal (Phoca groenlandica) body water, and to study whether these potential seasonal changes might bias results obtained using the doubly labelled water (DLW) method when measuring energy expenditure in animals with access to freshwater. Seasonal changes in the background levels of deuterium and oxygen-18 in the body water of four captive harp seals and in the freshwater pool in which they were kept were measured over a time period of 1 year. The seals were offered daily amounts of capelin and kept under a seasonal photoperiod of 69°N. Large seasonal variations of deuterium and oxygen-18 in the pool water were measured, and the isotope abundance in the body water showed similar seasonal changes to the pool water. This shows that the seals were continuously equilibrating with the surrounding water as a result of significant daily water drinking. Variations in background levels of deuterium and oxygen-18 in freshwater sources may be due to seasonal changes in physical processes such as precipitation and evaporation that cause fractionation of isotopes. Rapid and abrupt changes in the background levels of deuterium and oxygen-18 may complicate calculation of energy expenditure by use of the DLW method. It is therefore strongly recommended that analysis of seasonal changes in background levels of isotopes is performed before the DLW method is applied on (free-ranging) animals, and to use a control group in order to correct for changes in background levels.

Hooded seal (Cystophora cristata) pups ingest snow and seawater during their post-weaning fast.

The purpose of this study was to evaluate the importance of exogenous water intake (snow/seawater) in hooded seal (Cystophora cristata) pups during their post-weaning fast. In this study, five hooded seal pups had ad lib access to snow and seawater for the first 12 and last 21 days of their post-weaning fast, respectively. Total body water and water flux were determined during both exposure periods by use of the tritiated water method. Blood samples were collected to monitor changes in hematocrit, plasma urea and plasma osmolality. Body mass loss was on average 0.36 kg day-1. Average total body water changed from 15.7 to 11.4 L, while total water influx changed from 15 to 18 mL day-1 kg-1 during snow and seawater exposure, respectively. Of this influx an average of 35% can be attributed to metabolic water, while approximately 8% was due to respiratory water influx. Interestingly, 56 and 58% of the total water influx was due to snow and seawater ingestion, respectively, amounting to 8 mL day-1 kg-1 snow (counted as liquid water) and 10 mL day-1 kg-1 seawater. Based on the results of the plasma parameters it is concluded that fasting hooded seal pups maintain water balance and homeostasis when access to snow or seawater is permitted. It is further concluded that snow and seawater intake, in addition to metabolic and respiratory water, is important for maintenance of water balance and excretion of urea during the post-weaning fast of hooded seal pups.