Juan Jiang1, Margo P Emont2, Heejin Jun3, Xiaona Qiao4, Jiling Liao5, Dong-Il Kim3, Jun Wu6. 1. Life Sciences Institute, 210 Washtenaw Ave Rm 5115, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China. 2. Life Sciences Institute, 210 Washtenaw Ave Rm 5115, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA. 3. Life Sciences Institute, 210 Washtenaw Ave Rm 5115, University of Michigan, Ann Arbor, MI, 48109, USA. 4. Life Sciences Institute, 210 Washtenaw Ave Rm 5115, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai 200040, P.R.China. 5. Life Sciences Institute, 210 Washtenaw Ave Rm 5115, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Endocrinology and Metabolism, 2nd Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China. 6. Life Sciences Institute, 210 Washtenaw Ave Rm 5115, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address: wujunz@umich.edu.
Abstract
OBJECTIVE: Cinnamaldehyde (CA) is a food compound that has previously been observed to be protective against obesity and hyperglycemia in mouse models. In this study, we aimed to elucidate the mechanisms behind this protective effect by assessing the cell-autonomous response of primary adipocytes to CA treatment. METHODS: Primary murine adipocytes were treated with CA and thermogenic and metabolic responses were assessed after both acute and chronic treatments. Human adipose stem cells were differentiated and treated with CA to assess whether the CA-mediated signaling is conserved in humans. RESULTS: CA significantly activated PKA signaling, increased expression levels of thermogenic genes and induced phosphorylation of HSL and PLIN1 in murine primary adipocytes. Inhibition of PKA or p38 MAPK enzymatic activity markedly inhibited the CA-induced thermogenic response. In addition, chronic CA treatment regulates metabolic reprogramming, which was partially diminished in FGF21KO adipocytes. Importantly, both acute and chronic effects of CA were observed in human adipose stem cells isolated from multiple donors of different ethnicities and ages and with a variety of body mass indexes (BMI). CONCLUSIONS: CA activates thermogenic and metabolic responses in mouse and human primary subcutaneous adipocytes in a cell-autonomous manner, giving a mechanistic explanation for the anti-obesity effects of CA observed previously and further supporting its potential metabolic benefits on humans. Given the wide usage of cinnamon in the food industry, the notion that this popular food additive, instead of a drug, may activate thermogenesis, could ultimately lead to therapeutic strategies against obesity that are much better adhered to by participants.
OBJECTIVE:Cinnamaldehyde (CA) is a food compound that has previously been observed to be protective against obesity and hyperglycemia in mouse models. In this study, we aimed to elucidate the mechanisms behind this protective effect by assessing the cell-autonomous response of primary adipocytes to CA treatment. METHODS: Primary murine adipocytes were treated with CA and thermogenic and metabolic responses were assessed after both acute and chronic treatments. Human adipose stem cells were differentiated and treated with CA to assess whether the CA-mediated signaling is conserved in humans. RESULTS: CA significantly activated PKA signaling, increased expression levels of thermogenic genes and induced phosphorylation of HSL and PLIN1 in murine primary adipocytes. Inhibition of PKA or p38 MAPK enzymatic activity markedly inhibited the CA-induced thermogenic response. In addition, chronic CA treatment regulates metabolic reprogramming, which was partially diminished in FGF21KO adipocytes. Importantly, both acute and chronic effects of CA were observed in human adipose stem cells isolated from multiple donors of different ethnicities and ages and with a variety of body mass indexes (BMI). CONCLUSIONS: CA activates thermogenic and metabolic responses in mouse and human primary subcutaneous adipocytes in a cell-autonomous manner, giving a mechanistic explanation for the anti-obesity effects of CA observed previously and further supporting its potential metabolic benefits on humans. Given the wide usage of cinnamon in the food industry, the notion that this popular food additive, instead of a drug, may activate thermogenesis, could ultimately lead to therapeutic strategies against obesity that are much better adhered to by participants.
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