Saroglitazar, a novel dual PPAR-α/γ agonist, reverses high fat-low protein diet-induced metabolic and cognitive aberrations in C57BL/6J male mice

Dharavath, Ravinder Naik; Arora, Sangeeta; Kondepudi, Kanthi Kiran; Bishnoi, Mahendra; Chopra, Kanwaljit

doi:10.1016/j.lfs.2021.119191

Cited by 9 publications

(12 citation statements)

References 51 publications

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“…According to scientific reports, PPAR-α activation regulates glucose homeostasis metabolism by increasing insulin sensitivity in adipose and muscle tissue. Also, the role of this receptor in regulating the expression of several genes controlling β-cell function has been shown in scientific studies [ 27 , 28 ]. Major expression of the G protein-coupled receptor 119 (GPR119) gene occurs in intestinal L cells and pancreatic β cells [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Improved glycemic status, insulin resistance and inflammation after receiving oral oleoylethanolamide supplement in people with prediabetes: a randomized controlled trial

Pouryousefi

Javadi

Hashemipour

et al. 2022

Diabetol Metab Syndr

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Background The anti-inflammatory properties of cannabinoids have been shown. This study was conducted to assess effect of oleoylethanolamide (OEA) supplementation on glycemic status, insulin resistance (IR) and inflammatory factor in pre-diabetic individuals. Methods This double-blind randomized clinical trial was done at Qazvin University of Medical Sciences in which 46 pre-diabetic patients were divided into two equal groups and received one 125 mg OEA capsule in the intervention group (23 subjects) and 125 mg capsule containing wheat flour in placebo group daily for 8 weeks. After collecting demographic information, at the beginning and end of the study, the questionnaires of physical activity, 24-hour food recall were completed and blood glucose (BG), plasma insulin level, IR, hemoglobin A1c (HbA1c), and C-reactive protein (CRP) were measured. Statistical analysis was performed using SPSS software. Results At the beginning and end of the study, there was no significant difference between the two groups in terms of anthropometric indices, food intake and physical activity (P > 0.05). At the end of the study, consumption of OEA significantly reduced BS, insulin, IR, HbA1c, and CRP (P < 0.05). No significant change was observed in mentioned biochemical factors in placebo group (P > 0.05). Conclusions Given that OEA supplementation improved the glycemic status, IR and reduced the inflammatory factor, use of this supplement can be introduced as a useful supplement to control pre-diabetes status. Trial registration: The protocol of this clinical trial is registered with the Iranian Registry of Clinical Trials (http://www.IRCT.IR, identifier: IRCT20141025019669N16).

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Section: Discussionmentioning

confidence: 99%

Improved glycemic status, insulin resistance and inflammation after receiving oral oleoylethanolamide supplement in people with prediabetes: a randomized controlled trial

Pouryousefi

Javadi

Hashemipour

et al. 2022

Diabetol Metab Syndr

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“…Furthermore, the decline in behavioral and cognitive performance in Y‐maze assessment, particularly a decrease in exploratory time in the arms of the Y‐maze and percentage alternation in the arms suggest that HFD/STZ‐induced IR causes a decrease in ATP production needed for memory consolidation and reinforcement of newly formed synaptic connection during the learning phase of the assessment 46,69 . Therapeutically, PPAR has been described to contribute to the modulation of the secondary messengers of insulin signaling and PI3K/Akt/mTOR 70,71 . Hence, our findings showed that therapeutic use of FEN (PPARα) and PIO (PPARγ) as monotherapy and combined therapy may significantly improve insulin sensitivity, behavioral response, and cognitive function of the hippocampal neurons via the activation and upregulation of plasma membrane glycolipids and PI3K/Akt/mTOR pathways.…”

Section: Discussionmentioning

confidence: 66%

The synergistic ameliorative activity of peroxisome proliferator‐activated receptor‐alpha and gamma agonists, fenofibrate and pioglitazone, on hippocampal neurodegeneration in a rat model of insulin resistance

Idowu

Oluyomi

Faniyan

et al. 2022

Ibrain

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Insulin resistance (IR) is a risk factor for metabolic disorders and neurodegeneration. Peroxisome proliferator-activated receptor (PPAR) agonists have been proven to mitigate the neuronal pathology associated with IR. However, the synergetic efficacy of these agonists is yet to be fully described.Hence, we aimed to investigate the efficacy of PPARα/γ agonists (fenofibrate and pioglitazone) on a high-fat diet (HFD) and streptozotocin (STZ)-induced hippocampal neurodegeneration. Male Wistar rats (200 ± 25 mg/body weight [BW]) were divided into five groups. The experimental groups were fed on an HFD for 12 weeks coupled with 5 days of an STZ injection (30 mg/kg/BW, i.p) to induce IR. Fenofibrate (FEN; 100 mg/kg/BW, orally), pioglitazone (PIO; 20 mg/kg/BW, orally), and their combination were administered for 2 weeks postinduction. Behavioral tests were conducted, and blood was collected to determine insulin sensitivity after treatment. Animals were killed for assessment of oxidative stress, cellular morphology characterization, and astrocytic evaluation. HFD/STZ-induced IR increased malondialdehyde (MDA) levels and decreased glutathione (GSH) levels. Evidence of cellular alterations and overexpression of astrocytic protein was observed in the hippocampus. By contrast, monotherapy of FEN and PIO increased the GSH level (p < 0.05), decreased the MDA level (p < 0.05), and improved cellular morphology and astrocytic expression. Furthermore, the combined treatment led to improved therapeutic activities compared to monotherapies. In conclusion, FEN and PIO exerted a therapeutic synergistic effect on HFD/ STZ-induced IR in the hippocampus.

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“…The normal control group animals received 0.5% CMC throughout the study. The doses for SGZ and scopolamine were selected in accordance with the previously reported studies. , The experimental protocol is for 16 days. From day 1 to day 7, groups 3 and 5 received SGZ pretreatment, while group 4 received donepezil pretreatment.…”

Section: Methodsmentioning

confidence: 99%

“…It was approved for the treatment of diabetic dyslipidemia, diabetic retinopathy, and renal fibrosis . Besides, SGZ reversed the high-fat and low-protein diet-induced metabolic and cognitive aberrations in mice . SGZ exhibited protective potential in 6-OHDA-induced Parkinson’s disease and decreased neuroinflammation induced by maximal electroshock seizure (MES) .…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effect of Saroglitazar on Scopolamine-Induced Alzheimer’s in Rats: Insights into the Underlying Mechanisms

Sandeep Ganesh,

Konduri,

Kolusu

et al. 2023

ACS Chem. Neurosci.

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Alzheimer’s disease (AD) is one of the most prevalent and progressive neurodegenerative disorders, hallmarked by increased amyloid-β deposition and enhanced oxidative load in the brain, ensuing cognitive decline. The present study is aimed at elucidating the neuroprotective effect of saroglitazar, a dual peroxisome-proliferator-activated receptor (PPARα/γ) agonist used in the treatment of diabetic dyslipidemia, against memory impairment induced by intraperitoneal scopolamine injection. 30 male Wistar rats were randomly divided into the following five groups: (A) Veh + Veh, (B) SGZ + Veh, (C) Veh + SCOP, (D) DPZ + SCOP, and (E) SGZ + SCOP. Rats of the respective groups were pretreated with saroglitazar (10 mg/kg, p.o.) and donepezil (3 mg/kg, p.o.) once daily for 16 days. During the final 9 days of the study, a daily injection of scopolamine (3 mg/kg, i.p.) was administered to the respective groups. Adjacent to the scopolamine injection, behavioral tests such as the open field, Y maze, novel object recognition test, and Morris water maze were conducted to assess learning and memory. Additionally, biochemical parameters such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), nitric oxide (NO), malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), brain-derived neurotrophic factor (BDNF), β-amyloid levels, and NF-κB were measured in the hippocampus. The rats that received scopolamine injections showed significantly impaired short-term spatial and learning memory. This was associated with an increase in β-amyloid, iNOS, nitric oxide (NO), malondialdehyde, NF-κB, and TNF-α levels in the hippocampus of AD rats. On the other hand, saroglitazar has provided promising data on its protective role in cognition by protecting the BDNF, SOD, and GSH decline. As a result, saroglitazar was found to be a promising therapy in AD by upregulating the antioxidant status and cholinergic activity and preventing memory loss. Collectively, findings in the present study revealed that saroglitazar protected AD by suppressing scopolamine-mediated learning and memory deficits, oxidative stress, and cholinergic damage. Studying these mechanisms may conclude the protective role of saroglitazar against AD. However, further studies in transgenic animals will provide numerous insights into treatment mechanisms and contribute to developing a therapeutic intervention for AD.

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Saroglitazar, a novel dual PPAR-α/γ agonist, reverses high fat-low protein diet-induced metabolic and cognitive aberrations in C57BL/6J male mice

Cited by 9 publications

References 51 publications

Improved glycemic status, insulin resistance and inflammation after receiving oral oleoylethanolamide supplement in people with prediabetes: a randomized controlled trial

Improved glycemic status, insulin resistance and inflammation after receiving oral oleoylethanolamide supplement in people with prediabetes: a randomized controlled trial

The synergistic ameliorative activity of peroxisome proliferator‐activated receptor‐alpha and gamma agonists, fenofibrate and pioglitazone, on hippocampal neurodegeneration in a rat model of insulin resistance

Neuroprotective Effect of Saroglitazar on Scopolamine-Induced Alzheimer’s in Rats: Insights into the Underlying Mechanisms

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