Cover Story Current Issue

Weaning involves a dietary switch in mammals, progressively decreasing the reliance on the consumption of a fat-rich milk diet in favour of a carbohydrate-rich diet. Metabolic adaptation to this shift in macronutrient consumption is characterized by reduced hepatic gluconeogenesis, increased liver glycogen content, and changes in lipid metabolism. Such metabolic changes are supported by various nutritional, hormonal, and neuronal factors. Dietary changes during weaning are shown to drive β-cell proliferation and maturation, which is important for the optimal endocrine function of the pancreas. A switch from the nutrient sensor target of rapamycin (mTORC1) to the energy sensor 5′-adenosine monophosphate-activated protein kinase (AMPK) was found critical for functional maturation of β-cells. Furthermore, changes in the macronutrient composition during the weaning process drive alterations in the gut microbiome, which is essential for the development of immune tolerance. The major calcium absorption pathway also changes during weaning, from the paracellular pathway during the suckling stage to the vitamin D dependent transcellular pathway post-weaning. However, the factors that regulate these post-weaning metabolic adaptations are not fully understood.

Full text

 

Current Issue

Adropin expression reflects circadian, lipoprotein, and mitochondrial processes in human tissues.

Joseph R. Stevens, Clemence Girardet, Mingqi Zhou, Farah Gamie, ... Sophie Guyonnet

The clinical significance of interindividual variation in circulating adropin levels is unclear. To better understand adropin biology at the whole-body level, we surveyed transcriptional structures co-regulated with the Energy Homeostasis Associated (ENHO) gene encoding adropin across human tissues using Gene-Derived Correlations Across Tissues (GD-CAT). ENHO/adropin-related transcriptional structures with >1000 genes meeting the selection threshold (q<0.001) occurred in 11/20 tissues. While most reflect local relationships, liver ENHO/adropin-related structures are dominated by transcripts expressed across metabolic tissues (skeletal muscle, adipose tissues, thyroid). Relationships between liver ENHO/adropin expression and skeletal muscle mitochondrial function were corroborated using liver-specific knockout mice. Within-liver ENHO/adropin transcriptional structures reflect lipoprotein metabolism (e.g., APOC1, p=4.91x10-11; APOA1, p=8.03x10-9), confirmed by correlations between plasma concentrations of adropin and indices of lipoprotein metabolism in MAPT samples. Moreover, statin treatment which increases hepatic cholesterol efflux, reduces plasma adropin levels. The ENHO gene contains retinoic acid receptor-related orphan receptor response elements (RORE), suggesting circadian control. Pan-organ transcriptional structures with liver ENHO/adropin or RORC overlap, reflecting the liver clock. Strong, local relationships between ENHO/adropin and circadian genes were also observed in most non-hepatic tissues. ENHO/adropin expression widely reflects activation of oxidative metabolic pathways and suppression of ribosomal functions and cell division. Finally, hippocampal ENHO/adropin expression correlates strongly with Alzheimer’s disease risk genes identified by GWAS. In summary, activation of ENHO/adropin expression reflects cellular circadian and mitochondrial oxidative processes, but with inhibition of anabolic processes. Plasma adropin concentrations may thus reflect hepatic lipoprotein production and activation of metabolic stress responses across human tissues.

Articles in Press

Adropin expression reflects circadian, lipoprotein, and mitochondrial processes in human tissues.

Joseph R. Stevens, Clemence Girardet, Mingqi Zhou, Farah Gamie, ... Sophie Guyonnet

The clinical significance of interindividual variation in circulating adropin levels is unclear. To better understand adropin biology at the whole-body level, we surveyed transcriptional structures co-regulated with the Energy Homeostasis Associated (ENHO) gene encoding adropin across human tissues using Gene-Derived Correlations Across Tissues (GD-CAT). ENHO/adropin-related transcriptional structures with >1000 genes meeting the selection threshold (q<0.001) occurred in 11/20 tissues. While most reflect local relationships, liver ENHO/adropin-related structures are dominated by transcripts expressed across metabolic tissues (skeletal muscle, adipose tissues, thyroid). Relationships between liver ENHO/adropin expression and skeletal muscle mitochondrial function were corroborated using liver-specific knockout mice. Within-liver ENHO/adropin transcriptional structures reflect lipoprotein metabolism (e.g., APOC1, p=4.91x10-11; APOA1, p=8.03x10-9), confirmed by correlations between plasma concentrations of adropin and indices of lipoprotein metabolism in MAPT samples. Moreover, statin treatment which increases hepatic cholesterol efflux, reduces plasma adropin levels. The ENHO gene contains retinoic acid receptor-related orphan receptor response elements (RORE), suggesting circadian control. Pan-organ transcriptional structures with liver ENHO/adropin or RORC overlap, reflecting the liver clock. Strong, local relationships between ENHO/adropin and circadian genes were also observed in most non-hepatic tissues. ENHO/adropin expression widely reflects activation of oxidative metabolic pathways and suppression of ribosomal functions and cell division. Finally, hippocampal ENHO/adropin expression correlates strongly with Alzheimer’s disease risk genes identified by GWAS. In summary, activation of ENHO/adropin expression reflects cellular circadian and mitochondrial oxidative processes, but with inhibition of anabolic processes. Plasma adropin concentrations may thus reflect hepatic lipoprotein production and activation of metabolic stress responses across human tissues.

Save the Date

12th Helmholtz 
Diabetes Conference 
22-24. Sep, Munich

2022 impact factor: 6.6

You are what you eat

Here is a video of Vimeo. When the iframes is activated, a connection to Vimeo is established and, if necessary, cookies from Vimeo are also used. For further information on cookies policy click here.

Auf Werbeinhalte, die vor, während oder nach Videos von WEBSITE-URL eingeblendet werden, hat WEBSITE-URL keinen Einfluss. Wir übernehmen keine Gewähr für diese Inhalte. Weitere Informationen finden Sie hier.