Abstract

Excessive consumption of dietary fats leads to the deposition of unnecessary metabolites and multiple organ damage. Lipids, important key regulators of Hedgehog signaling, are involved in triggering fibrotic chronic kidney disease. The present study encompasses the assessment of renal morphofunctional modifications and alteration of lipid metabolism influencing the changes in gene expression of hedgehog signaling pathway genes. Fifteen male Rattus norvegicus of 200 ± 25 grams weight were equally divided into three groups: control (standard rat chow), D-1 (unsaturated high-fat diet) and D-2 (saturated high-fat diet). Animals were provided with respective diets and were followed for 16 weeks. Both HFD-fed groups did not show overall body weight gain as compared to the control. While significant downregulation of hedgehog pathway genes was found in fatty diet groups. In comparison with the control group, Shh, Gli1, Gli2, and Gli3 were downregulated after the consumption of both unsaturated and saturated fatty diets. Ihh and Smo exhibit a similar downregulation in the D-1 group, but an upregulation was detected in the D-2 group. D-2 group also had an increased serum urea concentration as compared to the control (P = 0.0023). Furthermore, renal histopathology revealed tubular necrosis, glomerular edema, glomerular shrinkage, and hypocellularity. Collagen deposition in both HFD groups marks the extent of fibrosis summary figure. Extravagant intake of dietary fats impaired normal kidney functioning and morphofunctionally anomalous kidney triggers on Hh signaling in adult rats. These anomalies can be linked to an escalated risk of chronic kidney disease in adults strongly recommending the reduced uptake of fatty diets to prevent impaired metabolism and renal lipotoxicity.

Highlights

  • The intrusion of extra dietary fats with intracellular lipids results in the deposition of detrimental lipids leading to inappropriate organelle functioning, cell damage, or even cell death [1]

  • Intake of high-fat diet leads to impaired lysosomal functioning and excessive deposition of phospholipids and cholesterol in renal tissues that lead to lipid metabolism alterations [7]

  • We investigated the morphofunctional changes associated with the kidney in response to chronic exposure to unsaturated and saturated fatty diets

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Summary

Introduction

The intrusion of extra dietary fats with intracellular lipids results in the deposition of detrimental lipids leading to inappropriate organelle functioning, cell damage, or even cell death [1]. The previous investigation on mice model have revealed that HFD consumption for sixteen weeks persuaded to lipid deposition in kidney and caused renal damage via albuminuria, interstitial fibrosis, and glomerulosclerosis [11]. The excessive consumption of fats can possibly escalate the body’s lipid content to abnormally high, disrupting the usual lipid metabolism These changes can have the potential to trigger on Hh signaling pathway in the kidney of anomalous subjects. This investigation was aimed at exploring the changes in the expressions of fundamental genes that are involved in the Hedgehog signaling cascade and to assess the extent of morphofunctional change sin kidney due to the consumption of a high-fat diet in the Murine model

Materials and Methods
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