Diabetes

THE TOXICOLOGy-METABOLISM LINK

Obesity &Cell Metabolism Assays

Research

for

metabolism and bRowninGExcess white adipose tissue causes deleterious health effects, while brown adipose tissue is beneficial to overall health. Inducible brown adipocytes, also known as beige, brown-in-white, or brite adipocytes, present a promising treatment for obesity, diabetes, and metabolic disorders. Researchers are using Seahorse XF technology for relevant assay testing conditions and parameters. The Seahorse XF Cell Mito Stress Test measures the key parameters of mitochondrial function: basal respiration, ATP-linked respiration, proton leak, maximal respiration, and spare respiratory capacity. The Seahorse XF Glycolysis Stress Test measures the key parameters of glycolytic function: glycolysis, glycolytic capacity, and glycolytic reserve.

Seahorse XF technology reveals Notch signaling inhibition increases fatty acid oxidation.

Murine white adipocytes

Bi P et al., (2014) Nat Med.

adipocytes derived from c2c12 cells

Sharma A et al., (2014) PLoS One.

Seahorse XF technology reveals a significant increase in exogenous palmitate oxidation in bone morphogenetic protein 6 (BMP)-stimulated cells.

Seahorse XF Cell Mito Stress Test reveals a link between rosiglitazone stimulation and metabolic profile in hMADs-derived brite adipocytes.

Rosiglitazone-deprived white and brite hMADs adipocytes

loft a et al., (2015) Genes. Dev.O

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Gold standaRd assays FoR measuRinG metabolic RePRoGRamminG

metabolism and substRate utilizationNutrients are critical to maintaining cellular homeostasis and have a significant effect on metabolism. Metabolic disorders can cause abnormal processing of various nutrients leading to metabolic stress. Seahorse XF technology provides the capability to test, analyze, and understand the collected data.

Seahorse XF Cell Mito Stress Test reveals an inhibition of spare respiratory capacity due to increased ER-mitochondrial interaction.

Murine hepatocytes

Arruda AP et al., (2014) Nat Med.

Murine myoblasts

Hamilton DL, et al., (2014) Diabetologia.

Seahorse XF technology reveals Beta-site APP-clearing enzyme 1 (BACE1)-induced reduction in glucose oxidation.

Seahorse XF technology reveals decreased glycolytic activity in response to high glucose.

bovine retinal pericytes

Trudeau k et al., (2011) Invest Ophthalmol Vis Sci.

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Gold standaRd assays FoR measuRinG metabolic RePRoGRamminG

3T3-L1 adipocytes

Hahn WS et al., (2014) Am J Physiol Endrocrinol Metab.

Murine macrophages

Freemerman AJ et al., (2014) J Biol Chem.

metabolism and inFlammationChronic inflammation and other immunological effects are linked to metabolic disorders. Researchers are using Seahorse XF technology to further their research into the connection between metabolic disorders and chronic inflammation.

Seahorse XF technology demonstrates the reduction of respiratory capacity in the presence of proinflammatory cytokines.

Seahorse XF Glycolysis Stress Test reveals that glucose transporter 1 (GLUT1) overexpression increases macrophage glycolytic capacity while reducing mitochondrial respiration.

Murine macrophages

Jais KA et al., (2014) Cell.

Seahorae XF Cell Mito Stress Test identifies heme oxygenase-1 (HO-1) gene requirement for metabolic programming of naïve macrophages.

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tHe woRld’s most adVanced metabolic analyzeRs

XF data in Publications There are over 2,000 references utilizing Seahorse XF technology published in leading journals such as nature and cell. Scientists are embracing Seahorse XF technology to identify metabolic phenotypes and reprogramming to target metabolic pathways for therapeutic purposes.

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measuRinG tHe Key PaRameteRs oF cell metabolismtRanslational diabetes and tHeRaPeuticsResearch into promising therapeutics may provide much needed cures for obesity, diabetes, and other metabolic disorders. Seahorse XF technology provides researchers the tools necessary for comprehensive investigations into disease progression and therapeutic candidates.

metabolism and isletsUsing a cell line model to mimic the in vivo environment is crucial to any experiment. Researchers are using Seahorse XF technology with various cell lines and types to best represent the in vivo conditions associated with metabolic syndromes.

Murine islets

kim yk et al., (2015) Diabetologia.

Human PBMCs

Czajka A et al., (2015) EbioMedicine.

Murine islets

Soleimanpour SA, et al., (2014) Cell.

Seahorse XF technology reveals a mitochondrial inner membrane protein (CRIf1) requirement for OXPHOS function in isolated islets.

Seahorse XF Cell Mito Stress Test reveals a decreased maximal respiration in patients with diabetic nephropathy and correlates with patient Bioenergetic Health Index (BHI).

Seahorse XF technology identifies a diabetes susceptibility gene requirement, Clec16a, for normal glucose-utilization in islets.

Seahorse XF technology reveals that caloric restriction improves metabolism in muscle from middle-aged rats.

Seahorse XF technology reveals treatment with Fexaramine, a farnesoid X receptor agonist, increased mitochondrial respiration.

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Rat muscle fibers

Chen CN et al., (2015) Am J Physiol Endocrinol Metab.

Murine stromal vascular fraction cells

Fang S et al., (2015) Nat Med.O

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Functional XF metabolic assaysThe MeTabolic SyndroMe and MeTaboliSM link

Metabolic syndromes are currently at pandemic levels and are a significant health risk to the general population. As one of the world’s leading causes of death and disability worldwide, these syndromes include insulin resistance, obesity, non-alcoholic fatty liver disease, cardiovascular disease, and inflammation. The connection between metabolism and metabolic syndromes is evident, regardless of whether the research focuses on a specific cell type or tissue origin, disease area, or signaling pathway.

Mitochondrial dysfunction has emerged as a common thread amongst metabolic syndromes. Research into metabolic profiles and changes provides insight into browning, substrate and nutrient utilization, and inflammation. These metabolic paradigms are leading to opportunities for translational and t herapeutic candidates. Seahorse XF technology provides the capability to examine the mechanisms that link functional metabolism with the abnormalities that result in clinical disease.

Metabolism

Cell Type

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GLUCOSE

GLUTAMATE

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FATTY ACIDLACTATE CITRATE

Acetyl-CoA

TCA

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(ECAR)

MITOCHONDRIAL RESPIRATION

(OCR)

GLUTAMATE

ETC

PYRUVATE

SubSTraTeS and MeTaboliSM

© 2016 All rights reserved. Seahorse Bioscience and the Seahorse logo are trademarks of Seahorse Bioscience Inc. The content in this brochure is for informational purposes only and may be subject to change without notice.

Gold Standard metabolic aSSaySmeasuRinG tHe Key PaRameteRs oF cell metabolism

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XFp Cell Energy Phenotype Profile

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XF Mito Fuel Flex Test ProfileMitochondrial Function

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Corporate Headquarters

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Seahorse XF Mito Fuel Flex Test ProfileMitochondrial Function

Seahorse XF Cell Energy Phenotype TestMetabolic Phenotype & Potential

Seahorse XF Glycolysis Stress Test ProfileGlycolytic Function

Seahorse XF Cell Mito Stress Test ProfileMitochondrial Respiration