Leptin receptor signaling is required for high-fat diet-induced atrophic gastritis in mice
نویسندگان
چکیده
BACKGROUND Obesity increases the risk for malignancies in various tissues including the stomach. Atrophic gastritis with precancerous lesions is an obesity-associated disease; however, the mechanisms that underlie the development of obesity-associated atrophic gastritis are unknown. Leptin is a hormone derived from stomach as well as adipose tissue and gastric leptin is involved in the development of gastric cancer. The aim of the current study is to investigate the involvement of leptin receptor signaling in the development of atrophic gastritis during diet-induced obesity. METHODS Male C57BL/6, ob/ob and db/db mice were fed a high-fat diet (HFD) or a control diet (CD) from 1 week to 5 months. Pathological changes of the gastric mucosa and the expression of molecules associated with atrophic gastritis were evaluated in these mice. RESULTS HFD feeding induced gastric mucosal hyperplasia with increased gastric leptin expression. Mucosal hyperplasia was accompanied by a higher frequency of Ki67-positive proliferating cells and atrophy of the gastric glands in the presence of inflammation, which increased following HFD feeding. Activation of ObR signaling-associated molecules such as ObR, STAT3, Akt, and ERK was detected in the gastric mucosa of mice fed the HFD for 1 week. The morphological alterations associated with gastric mucosal atrophy and the expression of Muc2 and Cdx2 resemble those associated with human intestinal metaplasia. In contrast to wild-type mice, leptin-deficient ob/ob mice and leptin receptor-mutated db/db mice did not show increased Cdx2 expression in response to HFD feeding. CONCLUSION Together, these results suggest that activation of the leptin signaling pathway in the stomach is required to develop obesity-associated atrophic gastritis.
منابع مشابه
Evaluation of Diabetogenic Mechanism of High Fat Diet in Combination with Arsenic Exposure in Male Mice
Obesity is a main reason of type 2 diabetes and also chronic exposure to arsenic (As)can produce diabetic symptoms. In previous studies, the association between high-fat dietand arsenic in the incidence of diabetes was found, but the role of beta cells activity, livermitochondrial oxidative stress, and hepatic enzymes (leptin, adiponectin and beta amylase)was unclear. Thus, present study was co...
متن کاملEvaluation of Diabetogenic Mechanism of High Fat Diet in Combination with Arsenic Exposure in Male Mice
Obesity is a main reason of type 2 diabetes and also chronic exposure to arsenic (As)can produce diabetic symptoms. In previous studies, the association between high-fat dietand arsenic in the incidence of diabetes was found, but the role of beta cells activity, livermitochondrial oxidative stress, and hepatic enzymes (leptin, adiponectin and beta amylase)was unclear. Thus, present study was co...
متن کاملEndothelial leptin receptor mutation provides partial resistance to diet-induced obesity.
Leptin, a polypeptide hormone produced mainly by adipocytes, has diverse effects in both the brain and peripheral organs, including suppression of feeding. Other than mediating leptin transport across the blood-brain barrier, the role of the endothelial leptin receptor remains unclear. We recently generated a mutant mouse strain lacking endothelial leptin receptor signaling, and showed that the...
متن کاملVagal plasticity the key to obesity
In their commentary on our article in Molecular Metabolism [1], Page et al. [2] propose the concept that leptin can act as a “double agent” e inhibiting food intake in lean animals, but promoting food intake in obese animals. This hypothesis stems from our finding that knocking out leptin receptor in vagal afferent neurons increases food intake and weight gain in low fat fed mice, while prevent...
متن کاملAstrocytic leptin-receptor knockout mice show partial rescue of leptin resistance in diet-induced obesity.
To determine how astrocytic leptin signaling regulates the physiological response of mice to diet-induced obesity (DIO), we performed metabolic analyses and hypothalamic leptin signaling assays on astrocytic leptin-receptor knockout (ALKO) mice in which astrocytes lack functional leptin receptor (ObR) signaling. ALKO mice and wild-type (WT) littermate controls were studied at different stages o...
متن کامل