Regulation of Autophagy-Related Protein and Cell Differentiation by High Mobility Group Box 1 Protein in Adipocytes

Abstract

High mobility group box 1 protein (HMGB1) is a molecule related to the development of inflammation. Autophagy is vital to maintain cellular homeostasis and protect against inflammation of adipocyte injury. Our recent work focused on the relationship of HMGB1 and autophagy in 3T3-L1 cells. In vivo experimental results showed that, compared with the normal-diet group, the high-fat diet mice displayed an increase in adipocyte size in the epididymal adipose tissues. The expression levels of HMGB1 and LC3II also increased in epididymal adipose tissues in high-fat diet group compared to the normal-diet mice. The in vitro results indicated that HMGB1 protein treatment increased LC3II formation in 3T3-L1 preadipocytes in contrast to that in the control group. Furthermore, LC3II formation was inhibited through HMGB1 knockdown by siRNA. Treatment with the HMGB1 protein enhanced LC3II expression after 2 and 4 days but decreased the expression after 8 and 10 days among various differentiation stages of adipocytes. By contrast, FABP4 expression decreased on the fourth day and increased on the eighth day. Hence, the HMGB1 protein modulated autophagy-related proteins and lipid-metabolism-related genes in adipocytes and could be a new target for treatment of obesity and related metabolic diseases.

High-fat diet enhances starvation-induced hyperactivity via sensitizing hunger-sensing neurons in Drosophila

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Proper regulation of food intake can be disrupted by sustained metabolic challenges such as high-fat diet (HFD), which may result in various metabolic disorders. Previously, we showed that starvation induced sustained hyperactivity, an exploratory component of food-seeking behavior, via a specific group of octopamingeric (OA) neurons (Yu et al, 2016). In the present study, we found that HFD greatly enhanced starvation-induced hyperactivity.

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“…We have previously reported that starvation induced hyperactivity in fruit flies Drosophila melanogaster, which facilitated the localization and acquisition of food and hence partly resembled food-seeking behavior (Yang et al, 2015;Yu et al, 2016). In this present study, we first asked whether HFD affected starvation-induced hyperactivity in fruit flies.…”

“…We have also identified a small subset of OA neurons in the fly brain that specifically regulate starvation-induced hyperactivity (Yu et al, 2016). Analogous to mammalian systems, a number of neural and hormonal cues are involved in the systemic control of nutrient metabolism and food intake.…”

“…Among them, Neuropeptide F (NPF), short NPF (sNPF), Leucokinin, and Allatostatin A (AstA), have been shown to regulate food consumption, all of which have known mammalian homologs that regulate food intake (Pool and Scott, 2014). In particular, starvation-induced hyperactivity is regulated by two classes of neuroendocrine cells (Yu et al, 2016). One is functionally analogous to pancreatic  cells and produce AKH upon starvation, whereas the other produce Drosophila insulin-like peptides (DILPs), resembling the function of pancreatic  cells.…”

“…One is functionally analogous to pancreatic  cells and produce AKH upon starvation, whereas the other produce Drosophila insulin-like peptides (DILPs), resembling the function of pancreatic  cells. These two classes of Drosophila hormones exert antagonistic functions on starvation-induced hyperactivity via the same group of OA neurons in the fly brain (Yu et al, 2016).…”