Dietary Fat-Accelerating Leptin Signaling Promotes Protumorigenic Gastric Environment in Mice

Excess of fat intake leads to obesity and causes a variety of metabolic diseases and cancer. We previously demonstrated that high-lard diet induces intestinal metaplasia, a precancerous lesion of the stomach mediated by leptin signaling. This study aims to investigate which kinds of dietary fat cause the intestinal metaplasia onset. We fed eight kinds of high-fat diets (HFDs) of animal or plant origin to mice evaluated their effect on gastric pathogenesis. Five types of dietary fat were divided according to their observed effects: Obese with high metaplasia (group I; beef tallow, lard, and hydrogenated coconut oil), non-obese with high metaplasia (group II; linseed oil), obese without metaplasia (group III; corn oil and olive oil), non-obese without metaplasia (group IV, soybean oil) and lean without metaplasia (group V; cocoa butter). The group I and II diets induced leptin, phosphorylated leptin receptor (ObR), signal transducer and activator 3 (STAT3), and increased intracellular β-catenin accumulation in the stomach. Moreover, mice fed these HFDs with 1-methyl-3-nitro-1-nitrosoguanidine (MNNG), a gastric carcinogen, and further accelerated dysplasia in the stomach. Lactobacillus occupancy in the stomach increased in all HFDs except hydrogenated coconut oil. Our findings suggest that HFDs inducing leptin signaling accelerate the enhancement of protumorigenic gastric microenvironment independent of body mass gain or microbiome changes

Assessment of meibomian gland morphology by noncontact infrared meibography in Shih Tzu dogs with or without keratoconjunctivitis sicca

[Objective] To investigate meibomian gland (MG) morphology by noncontact infrared meibography in Shih Tzu dogs with or without keratoconjunctivitis sicca (KCS). [Procedures] Fourteen eyes of 12 Shih Tzu dogs (mean age of 10.7 years, range of 7‐13 years) presented to Yakumo Animal Hospital or Triangle Animal Eye Clinic from 2011 to 2017 with clinical signs and a Schirmer tear test (STT) result consistent with KCS ( 15 mm/min served as healthy controls. Both groups of dogs underwent routine slitlamp biomicroscopy followed by noncontact infrared meibography of the upper eyelid with both desktop‐type and mobile‐type systems. [Results] Meibography revealed morphological abnormalities of MGs in 13 eyes of 11 dogs with KCS. The abnormalities included gland shortening in 64% and gland dropout in 64% of the 14 eyes in the KCS group. Morphological changes were also observed in MGs of 16 eyes of 10 dogs in the control group. These changes included shortening in 46% and dropout in 17.8% of the 28 eyes in the control group. Dropout was significantly more common in eyes with KCS than in control eyes (P < 0.01). [Conclusions] The frequency of MG abnormalities is increased in Shih Tzus with KCS compared with control animals. A reduced quality of the tear film associated with increased evaporation and reduced retention of tear fluid likely exacerbates the effects of a reduced tear volume in animals with aqueous deficiency

1,5-Anhydro-D-fructose Protects against Rotenone-Induced Neuronal Damage In Vitro through Mitochondrial Biogenesis

Mitochondrial functional abnormalities or quantitative decreases are considered to be one of the most plausible pathogenic mechanisms of Parkinson’s disease (PD). Thus, mitochondrial complex inhibitors are often used for the development of experimental PD. In this study, we used rotenone to create in vitro cell models of PD, then used these models to investigate the effects of 1,5-anhydro-D-fructose (1,5-AF), a monosaccharide with protective effects against a range of cytotoxic substances. Subsequently, we investigated the possible mechanisms of these protective effects in PC12 cells. The protection of 1,5-AF against rotenone-induced cytotoxicity was confirmed by increased cell viability and longer dendritic lengths in PC12 and primary neuronal cells. Furthermore, in rotenone-treated PC12 cells, 1,5-AF upregulated peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) expression and enhanced its deacetylation, while increasing AMP-activated protein kinase (AMPK) phosphorylation. 1,5-AF treatment also increased mitochondrial activity in these cells. Moreover, PGC-1α silencing inhibited the cytoprotective and mitochondrial biogenic effects of 1,5-AF in PC12 cells. Therefore, 1,5-AF may activate PGC-1α through AMPK activation, thus leading to mitochondrial biogenic and cytoprotective effects. Together, our results suggest that 1,5-AF has therapeutic potential for development as a treatment for PD

Additional file 3: Figure S1. of Leptin receptor signaling is required for high-fat diet-induced atrophic gastritis in mice

Alteration of index associated with obesity. Body weight (A), insulin, leptin, glucose and NEFA in sera (B) in CD- and HFD-fed WT, ob/ob and db/db mice were measured 1 week after feeding. Results were analyzed by the Kruskal Wallis test. *p < 0.01. (EPS 1473 kb

Additional file 2: Table S2. of Leptin receptor signaling is required for high-fat diet-induced atrophic gastritis in mice

Primers used for quantitative PCR. (DOCX 100 kb

Additional file 1: Table S1. of Leptin receptor signaling is required for high-fat diet-induced atrophic gastritis in mice

Antibody list: Antibodies used for western blotting and immunohistochemistry. (DOCX 127 kb