Cover Story Current Issue

The small intestine, as the primary site of nutrient absorption, integrates signals from dietary components and gut microbiota to coordinate systemic energy balance, metabolism, and glucose homeostasis alongside other tissues such as the pancreas, liver, and brain. Nuclear receptors represent one mechanism by which the intestinal epithelium senses and respond to dietary signals via transcriptional regulation of metabolic programs. The Peroxisome Proliferator Activated Receptors (PPARs), including PPARα, PPARδ, and PPARγ, are lipid-responsive nuclear hormone receptors. PPAR transcriptional activity is highly context-dependent, shaped by the availability and affinity of their lipid ligands and co-regulators as well as by cell and tissue types. Whereas PPARγ and PPARδ are established regulators of glucose homeostasis, acting in white adipose tissue, skeletal muscle, and liver to improve insulin sensitivity, PPARα has been primarily associated with hepatic lipid metabolism, where it promotes fatty acid transport, β-oxidation, and ketogenesis. Due to their roles in lipid metabolism and anti-inflammatory processes, selective PPAR agonists are being actively pursued as therapies in clinical and pre-clinical studies for metabolic diseases. Thus, it is critical to improve our understanding of the context-specific and tissue-specific effects of PPAR signaling.

Full text

 

Current Issue

DLST-driven metabolic alterations link skin to blood glucose: A translational study from mouse to human

Nsrein Ali, Syeda Tayyiba Rahat, Diana Motei, Mira Mäkelä, ... Seppo Vainio

To investigate the link between skin features and diabetes, we performed a multi-modal study combining a diabetic mouse model, a human pilot cohort, and keratinocyte response assays. Our goal was to identify molecular signatures in skin, cells, and sweat that correlate with glycemic control and could serve as early biomarkers of hyperglycemia. This integrative approach advances understanding of diabetes-associated dermatological changes and supports the development of targeted, non-invasive diagnostic tools for early detection.

Following glucose tolerance tests, proteomic and metabolomic profiling was performed. We identified dihydrolipoyl-succinyltransferase (DLST) as a promising biomarker whose protein and transcript levels consistently correlated with glycemic status across models. In HaCaT keratinocytes, DLST was found to drive metabolic reprogramming toward glutamine utilization as part of an antioxidant protective response. Chromatin immunoprecipitation assay revealed that Sp1 binds to the DLST promoter region, while functional studies, including Sp1 overexpression and knowdown, further confirmed that Sp1 regulates DLST at transcriptional level. Furthermore, DLST knockdown reproduced metabolic shifts in glutamine pathways, findings supported by proteomic analyses and stable isotopic flux analysis.

Reduced DLST expression in healthy skin corresponded with glutamine metabolism changes observed in keratinocytes upon oral glucose ingestion. While healthy skin and sweat displayed opposing metabolic trends, pre-type 2 diabetes samples showed aligned trends, suggesting sweat metabolomics could serve as an early systemic metabolic indicator.

These findings identify DLST as a glucose-responsive biomarker reflecting skin and sweat responses to systemic glucose, providing a foundation for the development of targeted, non-invasive diagnostic tools for early detection of diabetes.

Articles in Press

DLST-driven metabolic alterations link skin to blood glucose: A translational study from mouse to human

Nsrein Ali, Syeda Tayyiba Rahat, Diana Motei, Mira Mäkelä, ... Seppo Vainio

To investigate the link between skin features and diabetes, we performed a multi-modal study combining a diabetic mouse model, a human pilot cohort, and keratinocyte response assays. Our goal was to identify molecular signatures in skin, cells, and sweat that correlate with glycemic control and could serve as early biomarkers of hyperglycemia. This integrative approach advances understanding of diabetes-associated dermatological changes and supports the development of targeted, non-invasive diagnostic tools for early detection.

Following glucose tolerance tests, proteomic and metabolomic profiling was performed. We identified dihydrolipoyl-succinyltransferase (DLST) as a promising biomarker whose protein and transcript levels consistently correlated with glycemic status across models. In HaCaT keratinocytes, DLST was found to drive metabolic reprogramming toward glutamine utilization as part of an antioxidant protective response. Chromatin immunoprecipitation assay revealed that Sp1 binds to the DLST promoter region, while functional studies, including Sp1 overexpression and knowdown, further confirmed that Sp1 regulates DLST at transcriptional level. Furthermore, DLST knockdown reproduced metabolic shifts in glutamine pathways, findings supported by proteomic analyses and stable isotopic flux analysis.

Reduced DLST expression in healthy skin corresponded with glutamine metabolism changes observed in keratinocytes upon oral glucose ingestion. While healthy skin and sweat displayed opposing metabolic trends, pre-type 2 diabetes samples showed aligned trends, suggesting sweat metabolomics could serve as an early systemic metabolic indicator.

These findings identify DLST as a glucose-responsive biomarker reflecting skin and sweat responses to systemic glucose, providing a foundation for the development of targeted, non-invasive diagnostic tools for early detection of diabetes.

2025 Impact Factor: 6.3

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.