Similarities and differences in constipation phenotypes between Lep knockout mice and high fat diet-induced obesity mice

Abstract

CRISPR-Cas9-mediated leptin (Lep) knockout (KO) mice exhibited prominent phenotypes for constipation, even though they were not compared with other model animals. This study compared the stool excretion, gastrointestinal motility, histological structure, mucin secretion, and enteric nerve function in Lep KO and high fat diet (HFD)-treated mice to determine if there were differences in their phenotypes for constipation. Most obesity phenotypes, including fat weight, adipocyte size, expression of lipolytic proteins (HSL, perilipin, and ATGL), and glucose concentrations, were detected similarly in the Lep KO and HFD-treated mice. They showed a similar decrease in the excretion parameters, including the stool number, weight, and water content, while the same pattern was detected in the gastrointestinal motility and intestinal length. A similar decrease in the mucosal layer thickness, muscle thickness, ability for mucin secretion, and expression of water channel (aquaporin 3 and 8) genes was detected in the mid-colon of the Lep KO and HFD-treated mice, but the alteration rate in some levels was greater in the HFD-treated group than the Lep KO mice. On the other hand, the levels of c-kit, nNOS, NSE, and PGP9.5 expression for the enteric neurons and intestitial cells of Cajal (ICC) were remarkably lower in the mid-colon of the HFD-treated mice than in the Lep KO mice, but the level of most proteins in both groups remained lower than those in the control group. A similar alteration pattern in the expression of muscarinic acetylcholine receptors (mAChRs) and serotonin receptors was detected in the Lep KO and HFD-treated mice. These results suggest that most phenotypes for obesity-induced constipation were similarly detected in the Lep KO and HFD-treated mice, but there was a difference in the regulatory function of the enteric nervous system (ENS).

Inhibition of mammalian mtDNA transcription acts paradoxically to reverse diet-induced hepatosteatosis and obesity

“…1c,d ). We performed bomb calorimetry and found a higher energy content in faeces in mice on a chow diet in comparison with mice on HFD, consistent with results from other studies 16 , 17 . IMT treatment did not additionally alter the total energy content in faeces (Fig.…”

Dipterocarpus tuberculatus as a promising anti-obesity treatment in Lep knockout mice

“…Mice were maintained under specific pathogen-free (SPF) conditions at 23 ± 2°C and 50 ± 10% relative humidity (RH) under a daily light cycle (lights on at 08:00 h and off at 20:00 h). The genotype of Lep KO mice was identified using DNA-PCR, as previously reported in the literature (22,23).…”

Complement C3-Deficiency-Induced Constipation in FVB/N-C3em1Hlee/Korl Knockout Mice Was Significantly Relieved by Uridine and Liriope platyphylla L. Extracts

“…GI motility and length were measured using the methods described in previous studies [8,9]. At 24 h after the Urd and AEtLP administration, WT and C3 KO mice were fed a 0.5 mL charcoal meal (3% suspension of activated charcoal in 0.5% aqueous methylcellulose) (Sigma-Aldrich Co.).…”

“…2023, 24, 15757 2 of 24 chemicals and diet, were widely applied to produce animal models with constipation phenotypes. In most cases, the human-like constipation was successfully induced by the oral administration or subcutaneous injection of loperamide (Lop) hydrochloride as well as by the feeding of a low-fiber diet containing 41.5% cornstarch, 24.5% milk casein, 10.0% sucrose, 10.0% dextrin, 7.0% mineral mixture, 6.0% corn oil, and 1.0% vitamin mixture for 5 weeks [8][9][10][11]. Also, the phenotypes for constipation could be induced by treatment with opioids and carbon, although these methods are rarely used [12,13].…”