A novel peroxisome proliferator-activated receptor (PPAR)γ agonist, NIP-222, reduces urinary albumin excretion in streptozotocin-diabetic mice independent of PPARγ activation

Metabolism ◽  
2003 ◽  
Vol 52 (12) ◽  
pp. 1633-1637 ◽  
Author(s):  
Takashi Yotsumoto ◽  
Takeshi Naitoh ◽  
Tatsuro Kanaki ◽  
Maho Matsuda ◽  
Nobutomo Tsuruzoe
2020 ◽  
Vol 29 (2) ◽  
pp. 143-149
Author(s):  
SA Nøgaard ◽  
FW Sand ◽  
DB Sørensen ◽  
H Søndergaard

In mouse (Mus musculus) models of diabetic nephropathy (DN), one of the most important read-outs is the 24-h urinary albumin excretion (UAE). The 24-h urine collection is usually performed by single housing mice in metabolic cages on wire mesh without enrichment. This is known to be stressful for the mice. Therefore, it was investigated if shorter urine collections would be sufficient to get reliable assessments of albuminuria. Twenty-one diabetic (C57BLKS-Leprdb/db) and ten non-diabetic mice (C57BLKS-Leprdb/+) were placed in metabolic cages at 15 and 20 weeks of age (WoA) for 24 h. Urine samples were taken at 4, 6, 18 and 24 h and albumin and creatinine concentration were measured. Four- and 6-h UAE was found to correlate significantly with 24-h UAE. Furthermore, a significant correlation was found between 24-h UAE and albumin:creatinine ratio (ACR) in the 4-h sample. However, the strength of the correlation between ACR and 24-h UAE was weaker than between the 4- and 24-h UAE. This suggests that normalising to creatinine may not provide additional value to the 4-h urine collection. In conclusion, the strong correlation between 4- and 6-h UAE and 24-h UAE indicates that the collection period can be considerably reduced. This refinement could reduce stress and increase welfare of the db/db model and potentially be applied to other DN models


2009 ◽  
Vol 30 (2) ◽  
pp. 352-360 ◽  
Author(s):  
Rashmi Kumari ◽  
Lisa B Willing ◽  
Shyama D Patel ◽  
J Kyle Krady ◽  
William J Zavadoski ◽  
...  

Diabetes is an increased risk factor for stroke and results in increased brain damage in experimental animals and humans. The precise mechanisms are unclear, but our earlier studies in the db/db mice suggested that the cerebral inflammatory response initiating recovery was both delayed and diminished in the diabetic mice compared with the nondiabetic db/+ mice. In this study, we investigated the actions of the peroxisome proliferator-activated receptor (PPAR)-γ agonist darglitazone in treating diabetes and promoting recovery after a hypoxic-ischemic (H/I) insult in the diabetic ob/ob mouse. Male ob/+ and ob/ob mice received darglitazone (1 mg/kg) for 7 days before induction of H/I. Darglitazone restored euglycemia and normalized elevated corticosterone, triglycerides, and very-low-density lipoprotein levels. Darglitazone dramatically reduced the infarct size in the ob/ob mice at 24 h of recovery compared with the untreated group (30±13% to 3.3±1.6%, n=6 to 8) but did not show any significant effect in the ob/+ mice. Microglial and astrocytic activation monitored by cytokine expression (interleukin-1β and tumor necrosis factor-α) and in situ hybridization studies ( bfl1 and glial fibrillary acidic protein) suggest a biphasic inflammatory response, with darglitazone restoring the compromised proinflammatory response(s) in the diabetic mouse at 4 h but suppressing subsequent inflammatory responses at 8 and 24 h in both control and diabetic mice.


Author(s):  
Serena Stopponi ◽  
Yannick Fotio ◽  
Carlo Cifani ◽  
Hongwu Li ◽  
Carolina L Haass-Koffler ◽  
...  

Abstract Background and aims Andrographis paniculata is an annual herbaceous plant which belongs to the Acanthaceae family. Extracts from this plant have shown hepatoprotective, anti-inflammatory and antidiabetic properties, at least in part, through activation of the nuclear receptor Peroxisome Proliferator-Activated Receptor-gamma (PPAR γ). Recent evidence has demonstrated that activation of PPARγ reduces alcohol drinking and seeking in Marchigian Sardinian (msP) alcohol-preferring rats. Methods The present study evaluated whether A. paniculata reduces alcohol drinking and relapse in msP rats by activating PPARγ. Results Oral administration of an A. paniculata dried extract (0, 15, 150 mg/kg) lowered voluntary alcohol consumption in a dose-dependent manner and achieved ~65% reduction at the dose of 450 mg/kg. Water and food consumption were not affected by the treatment. Administration of Andrographolide (5 and 10 mg/kg), the main active component of A. paniculata, also reduced alcohol drinking. This effect was suppressed by the selective PPARγ antagonist GW9662. Subsequently, we showed that oral administration of A. paniculata (0, 150, 450 mg/kg) prevented yohimbine- but not cues-induced reinstatement of alcohol seeking. Conclusions Results point to A. paniculata-mediated PPARγactivation as a possible therapeutic strategy to treat alcohol use disorder.


Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 261
Author(s):  
Lieu Tran ◽  
Gerd Bobe ◽  
Gayatri Arani ◽  
Yang Zhang ◽  
Zhenzhen Zhang ◽  
...  

Peroxisome proliferator-activated receptor-γ2 gene Pro12Ala allele polymorphism (PPARG2 Pro12Ala; rs1801282) has been linked to both cancer risk and dietary factors. We conducted the first systematic literature review of studies published before December 2020 using the PubMed database to summarize the current evidence on whether dietary factors for cancer may differ by individuals carrying C (common) and/or G (minor) alleles of the PPARG2 Pro12Ala allele polymorphism. The inclusion criteria were observational studies that investigated the association between food or nutrient consumption and risk of incident cancer stratified by PPARG2 Pro12Ala allele polymorphism. From 3815 identified abstracts, nine articles (18,268 participants and 4780 cancer cases) covering three cancer sites (i.e., colon/rectum, prostate, and breast) were included. CG/GG allele carriers were more impacted by dietary factors than CC allele carriers. High levels of protective factors (e.g., carotenoids and prudent dietary patterns) were associated with a lower cancer risk, and high levels of risk factors (e.g., alcohol and refined grains) were associated with a higher cancer risk. In contrast, both CG/GG and CC allele carriers were similarly impacted by dietary fats, well-known PPAR-γ agonists. These findings highlight the complex relation between PPARG2 Pro12Ala allele polymorphism, dietary factors, and cancer risk, which warrant further investigation.


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