Plasma FGF21 concentrations, adipose fibroblast growth factor receptor-1 and β-klotho expression decrease with fasting in northern elephant seals

Abstract

Fibroblast growth factor (FGF)-21 is secreted from the liver, pancreas, and adipose in response to prolonged fasting/starvation to facilitate lipid and glucose metabolism. Northern elephant seals naturally fast for several months, maintaining a relatively elevated metabolic rate to satisfy their energetic requirements. Thus, to better understand the impact of prolonged food deprivation on FGF21-associated changes, we analyzed the expression of FGF21, FGF receptor-1 (FGFR1), β-klotho (KLB; a co-activator of FGFR) in adipose, and plasma FGF21, glucose and 3-hydroxybutyrate in fasted elephant seal pups. Expression of FGFR1 and KLB mRNA decreased 98% and 43%, respectively, with fasting duration. While the 80% decrease in mean adipose FGF21 mRNA expression with fasting did not reach statistical significance, it paralleled the 39% decrease in plasma FGF21 concentrations suggesting that FGF21 is suppressed with fasting in elephant seals. Data demonstrate an atypical response of FGF21 to prolonged fasting in a mammal suggesting that FGF21-mediated mechanisms have evolved differentially in elephant seals. Furthermore, the typical fasting-induced, FGF21-mediated actions such as the inhibition of lipolysis in adipose may not be required in elephant seals as part of a naturally adapted mechanism to support their unique metabolic demands during prolonged fasting.

The effects of metformin on fibroblast growth factor 19, 21 and fibroblast growth factor receptor 1 in high-fat diet and streptozotocin induced diabetic rats

“…Besides, gen analysis suggested that FGFR1 may be a regulator of adipogenesis by increasing fat cell numbers [27]. Moreover, our results confirmed the former hypothesis that the expression of FGFR1 was mediated by FGF21 circulating levels [28]. This research may provide an alternative to the problem of metformin therapy.…”

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

“…To determine whether the elevation in total adiponectin in dolphins on a C17:0-rich diet was preceded by an increase in FGF21, we utilized a commercial ELISA previously used to measure serum FGF21 in cattle ( 29 , 30 ). The serum FGF21 concentrations were highly variable among this study’s dolphin population (129–1599 pg/ml), but was within similar ranges reported for humans 21–5300 pg/ml ( 31 ), pregnant cows 15–1600 pg/ml ( 29 ), pigs 225–325 pg/ml ( 32 ), northern elephant seals ~100–500 pg/ml ( 33 ), and rhesus monkeys 10–325 pg/ml ( 34 ). Even though we observed no significant difference between FGF21 levels over time, FGF21 was highly correlated with the abundance of total adiponectin (Table 1 ).…”

Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease

“…For instance, MIR17HG , KL , and BCL2L11 have been shown involved in cell-survival, apoptosis, and cellular aging, respectively 22 - 24 . Genetic variants near KL have also been shown associated with fasting glucose levels as well 25 . TMEM18 is involved in cellular migration; HLA-DR5 and CMIP play crucial roles in immune mediated responses and have been implicated in various immunological disorders 26 , 27 .…”