About

Sander Kersten is associated with the Bronfenbrenner Center for Translational Research at Cornell University. The center assists faculty in developing translational research projects, providing support such as proposal preparation, training, technical support, and facilitating collaborative relationships. The center also offers workshops, summer institutes, and talks on current research topics related to translational research. While specific details about Professor Kersten's individual research focus or background are not provided in the page text, his affiliation with the BCTR indicates involvement in research that aims to translate scientific findings into practical applications, supporting faculty in their research endeavors.

Research topics

• Biology
• Chemistry
• Cell biology
• Medicine
• Biochemistry
• Internal medicine
• Bioinformatics
• Endocrinology
• Cardiology

Selected publications

• Effects of fenofibrate on angiopoietin-like 3/4/8 proteins and apolipoprotein A5

  Journal of Lipid Research · 2026-04-27 · 1 citations

  articleOpen access

  Fenofibrate and other fibrates are peroxisome proliferator-activated receptor alpha agonists that are used to lower plasma triglyceride (TG) levels. Although fibrates are effective in decreasing TG, their ability to reduce adverse cardiovascular events and cardiovascular mortality in clinical trials has been disappointing. Peroxisome proliferator-activated receptor alpha agonists influence the expression of dozens of genes, but the mechanisms by which they lower TG levels are incompletely understood. Apolipoprotein A5 (APOA5) and angiopoietin-like proteins 3, 4, and 8 (ANGPTL3/4/8) are important regulators of intravascular TG metabolism. To explore if their regulation might explain the TG-lowering effect of fibrates, we examined the impact of fenofibrate on the expression of APOA5 and the ANGPTL3/4/8 proteins in mice and humans. In WT mice, fenofibrate reduced plasma TG levels, increased Angptl4 and Angptl3 transcripts in the liver, and reduced Angptl8 and Apoa5 transcripts. Fenofibrate also decreased plasma APOA5 levels and increased levels of ANGPTL3, ANGPTL3/8, ANGPTL4/8, and the C-terminal domain of ANGPTL4 (CD-ANGPTL4). These changes would be predicted to increase rather than decrease TG levels. The TG reduction by fenofibrate was maintained in Apoa5-deficient mice, further indicating that APOA5 is not involved in TG lowering by fenofibrate. In humans, fenofibrate reduced TG without increasing APOA5 levels or reducing ANGPTL3/8 levels. In addition, fenofibrate treatment increased levels of ANGPTL3, ANGPTL4/8, and CD-ANGPTL4. The collective human and mouse data suggest that APOA5 and ANGPTL3/4/8 proteins do not mediate fenofibrate-induced TG lowering. Our findings are noteworthy because elevated levels of ANGPTL3, ANGPTL4/8, and CD-ANGPTL4 are associated with increased cardiovascular mortality.

  PublisherOA PDFDOI

• Blood-flow restriction resistance training improves skeletal muscle mitochondrial capacity and cardiovascular risk factors in type 2 diabetes

  Cell Metabolism · 2026-01-28

  articleOpen access

  Impaired muscle strength and mitochondrial functionality are hallmarks of type 2 diabetes (T2D). Conventional combined resistance/endurance exercise training has limited efficacy to simultaneously improve muscle function and metabolism. We examined whether low-load blood-flow restriction training (BFRT) increases both muscle strength and mitochondrial oxidative capacity in T2D. Over 12 weeks, BFRT and conventional resistance training (CREST) similarly improved muscle strength despite lower workload in BFRT. Uniquely, BFRT enhanced muscle and adipose tissue oxidative capacity and increased muscle mitochondrial content. Transcriptomic profiling revealed more pronounced changes, particularly in angiogenesis-linked pathways, upon BFRT. BFRT also preferentially led to reductions in visceral adipose tissue volume and waist circumference, whereas CREST more effectively decreased subcutaneous adipose tissue volume. Both interventions lowered resting heart rate and diastolic blood pressure. These findings position BFRT as a promising low-load exercising strategy to simultaneously improve mitochondrial oxidative capacity, muscle strength, and body composition in individuals with T2D. • BFRT matches CREST in muscle strength gains despite a markedly lower load • BFRT uniquely enhances skeletal muscle and adipose tissue oxidative capacity • BFRT induces greater transcriptional upregulation of angiogenesis-related pathways • BFRT exclusively reduces visceral adipose tissue volume Trinks et al. showed that blood-flow restriction training (BFRT) provides a low-load alternative to conventional resistance training (CREST), making it well suited for individuals with type 2 diabetes who have musculoskeletal limitations or reduced functional capacity because of promising effects on muscle strength, hypertrophy, mitochondrial capacity, and body composition.

  PublisherDOI

• Abstract 1898 Regulated inhibition of extracellular and intracellular lipolysis

  Journal of Biological Chemistry · 2025-05-01

  articleOpen access1st authorCorresponding

  Extracellular lipolysis is an essential step in the uptake of triglycerides by adipose tissue and is catalyzed by the enzyme lipoprotein lipase (LPL). Intracellular lipolysis is essential for mobilizing fatty acids, allowing them to be used internally or exported to other tissues. The key step in intracellular lipolysis is catalyzed by adipose triglyceride lipase (ATGL). The activities of LPL and ATGL are carefully regulated mainly through post-translational mechanisms. During fasting, LPL is inhibited in adipose tissue to prioritize the uptake of plasma triglycerides by other tissues.

  PublisherOA PDFDOI

• Regulation of Adipose Tissue Metabolism During Fasting

  Annual Review of Nutrition · 2025-05-06 · 6 citations

  reviewOpen accessSenior author

  There is widespread interest in fasting as a therapeutic or preventive regimen for improving health. This review provides an overview of the impact of fasting on adipose tissue metabolism, with special attention to sexually dimorphic regulation. During fasting, the storage of triacylglycerols in adipose tissue is inhibited via suppression of the extracellular lipolytic enzyme lipoprotein lipase. By contrast, the breakdown of stored triacylglycerols and subsequent release of fatty acids and glycerol in the blood are enhanced via stimulation of the intracellular lipolytic enzymes adipose triglyceride lipase and hormone-sensitive lipase. These metabolic alterations are driven by changes in humoral factors such as insulin, glucagon, corticosteroids, growth hormone, and catecholamines, as well as by neuronal pathways, and are mediated by transcriptional and posttranscriptional regulation of critical enzymes. Overall, fasting profoundly influences adipose tissue metabolism and leads to mobilization of stored triacylglycerols and the repartitioning of circulating triacylglycerols to nonadipose tissues.

  PublisherDOI

• Blueberries Reduce Palm Oil‐Induced Metabolic Endotoxemia in an In Vitro Human Intestinal‐Immune Cell Model

  Molecular Nutrition & Food Research · 2025-11-11 · 1 citations

  articleOpen access

  Metabolic endotoxemia (ME), a dietary lipid-induced increase in plasma LPS levels, is associated with cardiometabolic conditions. Accumulating evidence suggests an association between berry consumption and reduced endotoxemia. However, the underlying mechanisms remain unknown. This study examined the effects and potential mechanisms of blueberries, blackberries, and bananas on ME using an in vitro human intestinal-immune cell model. Palm oil with LPS was added to intestinal Caco-2 cells seeded on Transwell inserts, recapitulating dietary fat absorption. Higher levels of basolateral LPS were observed when Caco-2 cells were cotreated with palm oil and LPS compared to control and LPS, supporting lipid-induced LPS translocation. To examine the bioactivity of translocated LPS, THP1-Lucia nuclear factor kappa B (NF-κB) macrophages were exposed to basolateral conditioned media from Caco-2 cells, and NF-κB activation was assessed. Basolateral conditioned medium from Caco-2 cells cotreated with digested palm oil and LPS induced higher macrophage NF-κB activation compared to only palm oil. Interestingly, fruits reduced the palm oil + LPS-mediated NF-κB activation in macrophages. Transcriptomic and protein-level analyses suggest berries modulate the lipid-induced LPS translocation, likely via clathrin-mediated transcytosis with a minor chylomicron-mediated contribution. The anti-inflammatory effects of berry-rich diets may be mediated by preventing ME.

  PublisherDOI

• Weight cycling-induced hypothalamic and metabolic tissue immune remodeling is uncoupled from metabolic dysfunctions

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-27

  preprintOpen access

  Abstract Background Obesity-induced insulin resistance is associated with white adipose tissue (WAT) and liver inflammation, which are both mitigated by weight loss. However, most individuals undergoing weight loss will regain lost weight, resulting in weight cycling (WC), which may exacerbate metabolic dysfunctions. Here, we studied the immunometabolic impact of WC in mice. Methods C57BL/6J mice were exposed to two cycles of weight gain and weight loss by alternating between low (LFD) and high-fat diet (HFD) feeding. Animals were sacrificed when WC mice were weight stable for 10 weeks upon weight loss (WC-lean) and after a subsequent exposure to weight regain for 10 weeks (WC-obese), and compared to mice persistently fed LFD (LFD-lean) or HFD (HFD-obese). Results Body weight stabilized at a higher level in WC-lean mice after two weight gain/loss cycles compared to LFD-lean controls. While insulin resistance, metabolic tissue inflammation, and hepatic steatosis normalized between the two groups of lean mice, WC-lean mice exhibited features of WAT dysfunction. In the hypothalamus, inflammatory microglia were less abundant in WC-lean mice compared to LFD-lean mice, but mean individual microglial cell volume was larger. WC-obese mice stabilized at slightly lower weight compared with HFD-obese controls. Intriguingly, WC-obese mice exhibited increased WAT macrophages and reduced WAT and liver effector T cells compared to HFD-obese mice, whereas energy intake, body composition, whole-body insulin resistance and hepatic steatosis were similar. Conclusions Our results suggest that WC in mice differently impacts animals in the weight-stable lean and obese states. WC-lean mice display features of a novel body weight settling point, associated with hypothalamic inflammatory changes. However, metabolic dysfunctions were uncoupled from WC-induced metabolic tissue inflammation in WC-obese mice.

  PublisherOA PDFDOI

• Deficiency of the mitochondrial transporter SLC25A47 minimally impacts hepatic lipid metabolism in fasted and diet-induced obese mice

  Molecular Metabolism · 2025-01-01 · 1 citations

  articleOpen accessSenior authorCorresponding

  OBJECTIVE: The peroxisome proliferator-activated receptor-alpha (PPARα) plays a central role in lipid metabolism in the liver by stimulating the expression of hundreds of genes. Accordingly, regulation by PPARα could be a screening tool to identify novel genes involved in hepatic lipid metabolism. Previously, the mitochondrial transporter SLC25A47 was suggested to play a role in energy metabolism and liver-specific uncoupling, but further research is lacking. METHODS: We explored the potential role of SLC25A47 through in vitro studies and using mice overexpressing and lacking SLC25A47. RESULTS: SLC25A47 was identified as a PPARα-regulated and fasting-induced gene in human and mouse hepatocytes. Adenoviral-mediated overexpression of SLC25A47 minimally impacted metabolic parameters during fasting and high-fat feeding. During high-fat feeding, SLC25A47 ablation also did not influence any metabolic parameters, apart from a minor improvement in glucose tolerance. In fasted mice, SLC25A47 ablation was associated with modest, reproducible, and likely indirect reductions in plasma triglycerides and glycerol. SLC25A47 ablation did not influence energy expenditure. Depending on the nutritional status, metabolomic analysis showed modest alterations in plasma, liver, and hepatic mitochondrial levels of various metabolites related to amino acid metabolism, TCA cycle, and fatty acid metabolism. No major and consistent alterations in levels of specific metabolites were found that establish the substrate for and function of SLC25A47. CONCLUSION: Collectively, our results hint at a role of SLC25A47 in amino acid and fatty acid metabolism, yet suggest that SLC25A47 is dispensable for hepatic lipid homeostasis during fasting and high-fat feeding.

  PublisherDOI

• Target Populations for Novel Triglyceride-Lowering Therapies

  Journal of the American College of Cardiology · 2025-05-01 · 42 citations

  review
  PublisherDOI

• Drug-target Mendelian randomization analysis supports lowering plasma ANGPTL3, ANGPTL4, and APOC3 levels as strategies for reducing cardiovascular disease risk

  European Heart Journal Open · 2024-04-26 · 35 citations

  articleOpen accessSenior author

  Aims: APOC3, ANGPTL3, and ANGPTL4 are circulating proteins that are actively pursued as pharmacological targets to treat dyslipidaemia and reduce the risk of atherosclerotic cardiovascular disease. Here, we used human genetic data to compare the predicted therapeutic and adverse effects of APOC3, ANGPTL3, and ANGPTL4 inactivation. Methods and results: We conducted drug-target Mendelian randomization analyses using variants in proximity to the genes associated with circulating protein levels to compare APOC3, ANGPTL3, and ANGPTL4 as drug targets. We obtained exposure and outcome data from large-scale genome-wide association studies and used generalized least squares to correct for linkage disequilibrium-related correlation. We evaluated five primary cardiometabolic endpoints and screened for potential side effects across 694 disease-related endpoints, 43 clinical laboratory tests, and 11 internal organ MRI measurements. Genetically lowering circulating ANGPTL4 levels reduced the odds of coronary artery disease (CAD) [odds ratio, 0.57 per s.d. protein (95% CI 0.47-0.70)] and Type 2 diabetes (T2D) [odds ratio, 0.73 per s.d. protein (95% CI 0.57-0.94)]. Genetically lowering circulating APOC3 levels also reduced the odds of CAD [odds ratio, 0.90 per s.d. protein (95% CI 0.82-0.99)]. Genetically lowered ANGPTL3 levels via common variants were not associated with CAD. However, meta-analysis of protein-truncating variants revealed that ANGPTL3 inactivation protected against CAD (odds ratio, 0.71 per allele [95%CI, 0.58-0.85]). Analysis of lowered ANGPTL3, ANGPTL4, and APOC3 levels did not identify important safety concerns. Conclusion: Human genetic evidence suggests that therapies aimed at reducing circulating levels of ANGPTL3, ANGPTL4, and APOC3 reduce the risk of CAD. ANGPTL4 lowering may also reduce the risk of T2D.

  PublisherOA PDFDOI

• Metabolic effects of nuclear receptor activation in vivo after 28-day oral exposure to three endocrine-disrupting chemicals

  Archives of Toxicology · 2024-01-05 · 14 citations

  articleOpen access

  Environmental exposure to endocrine-disrupting chemicals (EDCs) can lead to metabolic disruption, resulting in metabolic complications including adiposity, dyslipidemia, hepatic lipid accumulation, and glucose intolerance. Hepatic nuclear receptor activation is one of the mechanisms mediating metabolic effects of EDCs. Here, we investigated the potential to use a repeated dose 28-day oral toxicity test for identification of EDCs with metabolic endpoints. Bisphenol A (BPA), pregnenolone-16α-carbonitrile (PCN), and perfluorooctanoic acid (PFOA) were used as reference compounds. Male and female wild-type C57BL/6 mice were orally exposed to 5, 50, and 500 μg/kg of BPA, 1000, 10 000, and 100 000 µg/kg of PCN and 50 and 300 μg/kg of PFOA for 28 days next to normal chow diet. Primary endpoints were glucose tolerance, hepatic lipid accumulation, and plasma lipids. After 28-day exposure, no changes in body weight and glucose tolerance were observed in BPA-, PCN-, or PFOA-treated males or females. PCN and PFOA at the highest dose in both sexes and BPA at the middle and high dose in males increased relative liver weight. PFOA reduced plasma triglycerides in males and females, and increased hepatic triglyceride content in males. PCN and PFOA induced hepatic expression of typical pregnane X receptor (PXR) and peroxisome proliferator-activated receptor (PPAR)α target genes, respectively. Exposure to BPA resulted in limited gene expression changes. In conclusion, the observed changes on metabolic health parameters were modest, suggesting that a standard repeated dose 28-day oral toxicity test is not a sensitive method for the detection of the metabolic effect of EDCs.

  PublisherOA PDFDOI

Frequent coauthors

• Michael Müller

  University of East Anglia

  167 shared

• Rinke Stienstra

  Radboud University Nijmegen

  115 shared

• Patrick C.N. Rensen

  67 shared

• Laeticia Lichtenstein

  University of Leeds

  60 shared

• Mark V. Boekschoten

  58 shared

• Nguan Soon Tan

  57 shared

• Guido J. E. J. Hooiveld

  Wageningen University & Research

  54 shared

• Anastasia Georgiadi

  Heinrich Heine University Düsseldorf

  54 shared

Education

• M.S., Human Nutrition

  Wageningen University

  1993

• Ph.D., Nutritional Biochemistry

  Cornell University

  1997