2025/11/28

SDT fatty Rat – Multisystem T2D Complications Model

SDT fatty rat multi-organ complications data for ATTD-ASIA 2025

This page summarizes SDT fatty rat data highlighted for ATTD-ASIA 2025. The SDT fatty rat is a translational model of type 2 diabetes that develops multi-organ complications affecting kidney, retina, heart, peripheral nerve, and histopathology endpoints.

This page is intended for preclinical and translational researchers. It summarizes non-clinical data and does not provide medical or treatment advice for patients.

Overview of key SDT fatty phenotypes

Diabetic Kidney Disease (hyperfiltration → GFR decline → fibrosis)
Early Diabetic Retinopathy (ERG deficits · GFAP gliosis)
HFpEF-like cardiomyopathy (E/A ratio · LVEDP)
Fully compatible with AI-based pathology platforms

Key Organ Phenotypes

SDT fatty rats develop multi-organ complications of type 2 diabetes, allowing integrated evaluation of kidney, retina, heart, peripheral nerve, and histopathological endpoints in a single translational model.

Kidney – DKD in SDT fatty rats

Source: Poster CKD Summit 2024 – FITC-sinistrin GFR curve + FibroNest fibrosis map.

Glycemic control and GFR decline

Sample Image – Dapagliflozin effect on hyperglycemia and GFR

Dapagliflozin strongly reduces hyperglycemia and prevents GFR decline in Unx SDT fatty rats — Fed glycemia (upper panel) and glomerular filtration rate (GFR; lower panel) in SD rats, sham-operated rats, or uninephrectomized (Unx) SDT fatty rats on a 0.3% salt diet without or with dapagliflozin for 10 weeks. Statistical significance: *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

Renal fibrosis assessment by FibroNest

Sample Image – FibroNest antifibrotic readout

FibroNest platform uncovers the antifibrotic effects of dapagliflozin in the renal cortex of Unx SDT fatty rats — Representative Sirius Red images and image analysis layers (upper panel), and phenotypic fibrosis composite scores (lower panel) assessed with PharmaNest's high-resolution quantitative digital pathology in SD rats, sham, or Unx SDT fatty rats. Statistical significance: *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

Hyperfiltration followed by >50% GFR decline.
Glomerulosclerosis, tubular injury, and renal fibrosis.
Responds to SGLT2 inhibitors (SGLT2i), GLP-1 receptor agonists (GLP-1RA), and ACE inhibitors (ACEi) in this preclinical model.

Download poster: CKD Summit 2024 (PDF)

Retina – Early Diabetic Retinopathy (DR)

Source: ARVO 2018 – ERG deficits and GFAP gliosis.

Electroretinography (ERG) deficits

Sample Image – Retinal neurologic dysfunction

Electroretinography demonstrates retinal neurologic dysfunction in Unx SDT fatty rats from 12 weeks of age — A-wave (panel A; photoreceptor response) and B-wave (panel B; inner retinal cell activity) during a standard scotopic ERG recording to a bright white flash (0 log cd·s/m²). Amplitudes (panel C) and implicit times (panel D) of the oscillatory potentials (OPs, reflecting inner retinal function) extracted from scotopic responses. Statistical significance: *p<0.05 and ***p<0.001 vs Unx SD control.

Reactive gliosis in retina

Sample Image – GFAP/Vimentin gliosis

ERG deficits (A-wave, B-wave, oscillatory potentials).
GFAP and vimentin-positive gliosis indicating Müller cell activation.
Retinal vascular dilation and remodeling consistent with early DR.

Download poster: ARVO 2018 – Briand et al. (PDF)

Heart – HFpEF-like cardiomyopathy

Source: Mini-oral HFpEF data – E/A ratio decline and LVEDP elevation.

Cardiac function

Sample Image – Liraglutide effect on HFpEF-like phenotype

Liraglutide improves HFpEF in SDT fatty rats — Representative data indicating an HFpEF-like phenotype in SDT fatty rats and the effect of liraglutide on diastolic function parameters.

Preserved ejection fraction (EF) with diastolic dysfunction.
Elevated left ventricular end-diastolic pressure (LVEDP).
Responds to GLP-1 agonists such as liraglutide in this preclinical model.

Download mini-oral presentation (PDF)

AI-based Pathology – NephroPath, PEMP, FibroNest

Source: ASN 2024 – NephroPath, PEMP, and FibroNest overlays.

NephroPath AI – glomerular and tubular analysis

Sample Image – NephroPath AI readout

Nephropath AI demonstrates that dapagliflozin reduces tubuli impairment and glomerulosclerosis in Unx SDT fatty rats — Representative raw PAS staining and NephroPath AI multi-class prediction images (upper panel), and quantification of atrophic and dilated tubuli and sclerotic glomeruli (lower panel) in SD rats, sham, or Unx SDT fatty rats on a 0.3% salt diet without or with dapagliflozin for 10 weeks. Statistical significance: *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

PEMP – podocyte effacement analysis

Sample Image – PEMP podocyte readout

PEMP reveals that dapagliflozin improves podocyte effacement in Unx SDT fatty rats — Representative images of double staining for podocin/integrin α3 and maximum intensity projection with color coding for depth (left panel). Filtration Slit Length (FSL) and Filtration Slit Density (FSD), determined by PEMP (right panel), in SD rats, sham, or Unx SDT fatty rats. Statistical significance: *p<0.05, **p<0.01, ****p<0.0001.

FibroNest – fibrosis depth and volume mapping

Sample Image – FibroNest antifibrotic assessment

NephroPath – glomerular and tubular lesion analysis.
PEMP – quantitative assessment of podocyte effacement (FSL, FSD).
FibroNest – fibrosis depth and volume mapping in renal cortex.

Download poster: ASN Kidney Week 2024 – SDT fatty rat (PDF)

Nerve – Peripheral Neuropathy (NF-L)

Source: ATTD-ASIA 2025 Poster – NF-L reduction by dapagliflozin.

Peripheral neuropathy biomarker NF-L

Sample Image – NF-L (plasma neurofilament light chain)

Dapagliflozin lowers NFLC, a marker of neuropathy, another comorbidity observed in the Unx SDT fatty rat

NF-L (plasma neurofilament light chain) changes in Unx SDT fatty rats — Representative pictures of PGP9.5 immunostaining (A), electrocardiogram (B-D), thermal sensitivity assessed with the Hargreaves test (E) and NFLC plasma levels (F) in Sprague Dawley, SDT fatty sham or Unx SDT fatty rats treated without or with dapagliflozin. *p<0.05 and ** p<0.01

NF-L elevation indicates peripheral nerve injury in the Unx SDT fatty rat.
Dapagliflozin lowers NF-L in this model, suggesting improvement of neuropathy-related endpoints.
Neuropathy appears as an additional comorbidity alongside nephropathy and retinopathy in SDT fatty rats.

Download poster: ATTD Asia 2025 poster (PDF)

Key R&D partners for SDT fatty studies

Organ-focused CRO and imaging partners

Physiogenex (France) – DKD, HFpEF, and metabolic complications.

Cardiomedex (France) – Cardiac imaging, HFpEF characterization, and cardiometabolic phenotyping.

AI pathology partners – Aiosyn, Nipoka, PharmaNest, and others.

These partners play a central role in generating and validating SDT fatty rat data for global pharmaceutical R&D.

Applications

DKD progression and renoprotective drug evaluation.
HFpEF and cardiorenal axis studies.
Early DR neurovascular research.
AI pathology validation and digital biomarker development.

ATTD-ASIA 2025 e-Poster information

Title:
SGLT2 INHIBITION IMPROVES GLYCEMIC CONTROL, DIABETIC NEPHROPATHY AND NEUROPATHY IN THE SPONTANEOUSLY DIABETIC TORII FATTY RAT, A TRANSLATIONAL MODEL OF TYPE 2 DIABETES

Authors:
François Briand¹, Estelle Grasset¹, Takeshi Ohta², Masami Shinohara³, Caroline Dubroca⁴, Thierry Sulpice^1,4

¹Physiogenex, FRANCE
²Graduate School of Agriculture, Kyoto University, JAPAN
³CLEA Japan Inc, JAPAN
⁴Cardiomedex, FRANCE

This work will be presented as an e-Poster at ATTD-ASIA 2025.
Please search for “SDT fatty” or “SGLT2 inhibition” in the e-Poster system.

FAQ – SDT fatty rat and ATTD-ASIA 2025 data

Q1. What is the SDT fatty rat model?: The Spontaneously Diabetic Torii (SDT) fatty rat is a translational model of type 2 diabetes that develops multi-organ complications, including diabetic kidney disease, early diabetic retinopathy, HFpEF-like cardiomyopathy, and peripheral neuropathy.
Q2. Which organs and endpoints are covered on this page?: This page highlights kidney (DKD), retina (early DR), heart (HFpEF-like cardiomyopathy), peripheral nerve (neuropathy, NF-L), and AI-based pathological endpoints (NephroPath, PEMP, FibroNest) in SDT fatty rats.
Q3. Are these data clinical or preclinical?: All data presented here are preclinical, obtained in SDT fatty rats. They are intended for translational and drug discovery research and do not represent clinical efficacy or safety in humans.
Q4. Which drug classes have been evaluated in SDT fatty rats?: The model has been used to evaluate SGLT2 inhibitors, GLP-1 receptor agonists, ACE inhibitors, and other cardiometabolic interventions, focusing on their effects on DKD, HFpEF-like phenotypes, neuropathy markers, and histopathological endpoints.
Q5. How is AI-based pathology used in this model?: AI platforms such as NephroPath, PEMP, and FibroNest are applied to kidney sections to quantify glomerulosclerosis, tubular injury, podocyte effacement, and renal fibrosis, enabling reproducible digital biomarker development.
Q6. How can I access detailed posters and datasets?: Selected posters and presentations (CKD Summit 2024, ARVO 2018, ASN Kidney Week 2024, HFpEF mini-oral) can be downloaded from this page. For additional data or collaboration, please contact CLEA Japan and partner CROs listed above.
Q7. How can I collaborate or run studies using the SDT fatty model?: For collaboration, joint studies, or access to the SDT fatty model, please use the inquiry form at the bottom of this page. Confidential discussions can be arranged upon request.

Contact

For collaboration, joint studies, or model access, please contact CLEA Japan and our partner CROs using the inquiry form below.
Confidential discussion available upon request.

SDT fatty Rat – Multisystem T2D Complications Model