Feeding a Modified Fish Diet to Bottlenose Dolphins Leads to an Increase in Serum Adiponectin and Sphingolipids

Abstract

Feeding a modified fish diet has been suggested to improve insulin sensitivity in bottlenose dolphins; however, insulin sensitivity was not directly measured. Since demonstrating an improvement in insulin sensitivity is technically difficult in dolphins, we postulated that directional changes in the hormone axis: fibroblast growth factor 21 (FGF21)/Adiponectin/Ceramide (Cer), could provide further support to this hypothesis. We measured 2-h post-prandial serum FGF21, total adiponectin, percent unmodified adiponectin, ceramide, and sphingosine levels from dolphins fed a diet rich in heptadecanoic acid (C17:0) over 24 weeks. Serum FGF21 was quantified by ELISA with an observed range of 129–1599 pg/ml, but did not significantly change over the 24-week study period. Total adiponectin levels (mean ± SD) significantly increased from 776 ± 400 pmol/ml at week 0 to 1196 ± 467 pmol/ml at week 24. The percent unmodified adiponectin levels (mean ± SD) decreased from 23.8 ± 6.0% at week 0 to 15.2 ± 5.2% at week 24. Interestingly, although FGF21 levels did not change, there was a good correlation between FGF21 and total adiponectin (ρ = 0.788, P < 0.001). We quantified the abundances of serum ceramides and sphingosines (SPH) because adiponectin has a defined role in sphingolipid metabolism through adiponectin receptor-mediated activation of ceramidases. The most abundant ceramide in dolphin sera was Cer 24:1 comprising 49% of the ceramides measured. Significant reductions were observed in the unsaturated Cer 18:1, Cer 20:1, and Cer 24:1, whereas significant increases were observed in saturated Cer 22:0, Cer 24:0, and Cer 26:0. However, total serum ceramides did not change. Significant elevations were detected for total sphingosine, dihydrosphingosine, sphingosine-1-phosphate, and dihydrosphingosine-1-phosphate. Proteomic analysis of the serum proteins revealed few changes in serum proteins over the study period. In conclusion, shifting the dolphin diet to fishes rich in odd chain saturated fatty acids, such as C17:0, resulted in increased serum levels of the insulin sensitizing hormone adiponectin and serum SPH consistent with an insulin-sensitizing phenotype. It is still unclear whether FGF21 plays a role in the regulation of adiponectin in dolphins, similar to that shown in laboratory animal models.

The Role of Ceramides in Diabetes and Cardiovascular Disease Regulation of Ceramides by Adipokines

“…Blocking ceramide production with SPT inhibitor myriocin in DIO mice led to increased levels of circulating high molecular weight adiponectin ( 59 ). This inverse relationship between adiponectin and ceramides has also been shown in rats ( 155 , 156 ) and dolphins.…”

New Technologies for Monitoring Marine Mammal Health

“…Another example was a study investigating a dolphin condition similar to human metabolic syndrome using serum lipid profiles between two groups of dolphins, where high or low insulin were analyzed. The study found differences in phospholipid fatty acids in the two groups, which may play a role in the susceptibility to or development of an insulin-resistant-like state: the proteomic analysis of dolphin serum showed correlation of changes in the fatty acids with an insulin-sensitizing phenotype (Sobolesky et al, 2016).…”

“…In a parallel study supported by proteomic analysis, differences in serum lipid profiles between two groups of dolphins, with high or low insulin, found differences in phospholipid fatty acids. Shifting the dolphin diet to fish rich in odd chain saturated fatty acids, such as C17:0, resulted in increased serum levels of the insulin-sensitizing hormone adiponectin and serum sphingosines consistent with an insulinsensitizing phenotype (Sobolesky et al, 2016). A better understanding of the networks activated by the mechanisms regulating adiponectin in dolphins could aid research of metabolic syndrome and diabetes affecting human populations.…”

Proteomic Analysis of Non-depleted Serum Proteins from Bottlenose Dolphins Uncovers a High Vanin-1 Phenotype

“…Parallel reaction monitoring was previously utilized to measure one of the 11 proteins, adiponectin, from Table 1 . Dolphin (human-care and free-ranging) serum concentrations of adiponectin measured by reaction monitoring 22 26 41 range between 2.3–47.9 μg/ml. Adiponectin concentrations, measured by reaction monitoring in humans, range between 0.02 μg/ml and 3 μg/ml 42 43 .…”

“…Many insightful studies of marine mammal physiology and health have focused on oxygen transport, antioxidant, metabolic, and clinical laboratory-relevant proteins in the blood; however, comparative studies describing the circulating serum proteome in marine mammals have not been extensively interrogated for novel serum phenotypes that could underlie significant alternative mechanisms of protection and/or metabolic regulation. To extend the discovery of phenotypic determinants in the serum that may promote the ability of marine mammals to counter stress, we created a normalized spectral abundance factor rank-list of high abundance serum proteins from bottlenose dolphins ( Tursiops truncatus ) 22 alongside undepleted human and pig serum proteomes generated in-house. Outlier ranked proteins were listed and one of the outlier proteins, Vanin-1, was chosen to validate the rank differences.…”