Cover Story Current Issue

Glucose is a ubiquitous and essential source of energy for all living organisms. Although mammals have evolved ways to convert other nutritional molecules to ATP, the preference for dietary glucose appears to be preserved. In rodents, the immediate detection of ingested glucose potently reinforces intake, hierarchically organizing behaviors towards glucose-yielding substances, and away from other types of food including other sugars. Taste is the primary sense linked to nutrient selection. Until recently, it was thought that most mammalian species utilize a single broadly tuned receptor to detect all simple sugars. Indeed, this “sweet” receptor, which comprises a heterodimer of the T1R2 and T1R3 proteins, binds multiple natural sugars (e.g., glucose, fructose, sucrose, maltose), as well as various other chemicals that yield little to no energy (e.g., low calorie sweeteners, sugar alcohols) and some d-amino acids. The neural signal originating from the sweet receptor is hardwired into brain circuits that drive eating and drinking behaviors, but it is an unreliable indicator of nutrient quality and quantity.

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Current Issue

Diet and temperature interactively impact brown adipose tissue gene regulation controlled by DNA methylation

Tobias Hagemann, Anne Hoffmann, Kerstin Rohde-Zimmermann, Helen Broghammer, ... Juliane Weiner

 

Controlling brown adipose tissue (BAT) plasticity offers potential for novel obesity therapies. DNA methylation is closely linked to thermogenic and metabolic pathways and thereby influences BAT function. How metabolic state and cold exposure interact to shape methylation-dependent BAT gene regulation was investigated.

Five-week-old mice were fed either chow for 11 weeks (lean) or high-fat diet for 22 weeks to induce obesity (DIO), after which cold exposure was applied for seven days. BAT transcriptomes (RNAseq) and methylomes (RRBS) were generated, and differentially methylated and expressed genes (DMEGs) showing metabolic state–dependent cold responses were identified. Pathway enrichment, epigenetic regulator screening, and transcription factor (TF) motif analyses were performed. DNA methylation was experimentally modulated in vitro to validate selected gene expression responses.

A total of 1,364 differentially expressed genes (DEGs) were uniquely affected by the interaction of metabolic state and cold, with most downregulated in DIO mice. Sixty-five DMEGs (4% of DEGs) showed metabolic state–specific responses to cold. In DIO mice, DMEGs were enriched in pathways associated with mitochondrial dysfunction, altered lipid metabolism, neuroendocrine signaling, and stress responses. Several epigenetic regulators, including Tet2, Dnmt3a, and Apobec1, exhibited metabolic state- and cold-dependent expression, and TF-motif analyses highlighted roles for Ahr::Arnt and Foxn1. In vitro assays confirmed that DNA methylation influences expression of thermogenic genes.

These findings provide the first evidence that the epigenetic cold response of BAT differs by metabolic condition. BAT remodeling is shaped by coordinated transcriptional and epigenetic mechanisms integrating environmental and metabolic cues.

 

 

Articles in Press

Diet and temperature interactively impact brown adipose tissue gene regulation controlled by DNA methylation

Tobias Hagemann, Anne Hoffmann, Kerstin Rohde-Zimmermann, Helen Broghammer, ... Juliane Weiner

 

Controlling brown adipose tissue (BAT) plasticity offers potential for novel obesity therapies. DNA methylation is closely linked to thermogenic and metabolic pathways and thereby influences BAT function. How metabolic state and cold exposure interact to shape methylation-dependent BAT gene regulation was investigated.

Five-week-old mice were fed either chow for 11 weeks (lean) or high-fat diet for 22 weeks to induce obesity (DIO), after which cold exposure was applied for seven days. BAT transcriptomes (RNAseq) and methylomes (RRBS) were generated, and differentially methylated and expressed genes (DMEGs) showing metabolic state–dependent cold responses were identified. Pathway enrichment, epigenetic regulator screening, and transcription factor (TF) motif analyses were performed. DNA methylation was experimentally modulated in vitro to validate selected gene expression responses.

A total of 1,364 differentially expressed genes (DEGs) were uniquely affected by the interaction of metabolic state and cold, with most downregulated in DIO mice. Sixty-five DMEGs (4% of DEGs) showed metabolic state–specific responses to cold. In DIO mice, DMEGs were enriched in pathways associated with mitochondrial dysfunction, altered lipid metabolism, neuroendocrine signaling, and stress responses. Several epigenetic regulators, including Tet2, Dnmt3a, and Apobec1, exhibited metabolic state- and cold-dependent expression, and TF-motif analyses highlighted roles for Ahr::Arnt and Foxn1. In vitro assays confirmed that DNA methylation influences expression of thermogenic genes.

These findings provide the first evidence that the epigenetic cold response of BAT differs by metabolic condition. BAT remodeling is shaped by coordinated transcriptional and epigenetic mechanisms integrating environmental and metabolic cues.

 

 

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13th
Helmholtz Diabetes Conference 

Munich, 21-23. Sep 2026

2024 impact factor: 6.6

You are what you eat

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