Caffeine attenuated ER stress-induced leptin resistance in neurons.
Exposing the endoplasmic reticulum (ER) to stress causes the accumulation of unfolded proteins, and subsequently results in ER stress. ER stress may be involved in various disorders such as obesity, diabetes, and neurodegenerative diseases. Leptin is an important circulating hormone, that inhibits food intake and accelerates energy consumption, which suppresses body weight gain. Recent studies demonstrated that leptin resistance is one of the main factors involved in the development of obesity. We and other groups recently reported the role of ER stress in the development of leptin resistance. Therefore, identifying drugs that target ER stress may be a promising fundamental strategy for the treatment of obesity. In the present study, we investigated whether caffeine could affect ER stress and the subsequent development of leptin resistance. We showed that caffeine exhibited chaperone activity, which attenuated protein aggregation. Caffeine also inhibited the ER stress-induced activation of IRE1 and PERK, which suggested the attenuation of ER stress. Moreover, caffeine markedly improved ER stress-induced impairments in the leptin-induced phosphorylation of STAT3. Therefore, these results suggest caffeine may have pharmacological properties that ameliorate leptin resistance by reducing ER stress.
Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Toru
T
Hosoi
Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Keisuke
K
Toyoda
Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Kanako
K
Nakatsu
Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan. Electronic address: ozawak@hiroshima-u.ac.jp.
Koichiro
K
Ozawa
D002110:Caffeine / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006358:Hot Temperature; D006801:Humans; D020738:Leptin / Q000502:physiology*; D009113:Muramidase / Q000737:chemistry; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D066329:Protein Aggregates; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D056811:Unfolded Protein Response
D020738:Leptin; D066329:Protein Aggregates; D054411:Receptors, Leptin; D002110:Caffeine; D009113:Muramidase
Caffeine; Endoplasmic reticulum stress; Leptin; STAT3