Flavonoids are a class of plant and fungus secondary metabolites and are the most common group of polyphenolic compounds in the human diet. In recent studies, flavonoids have been shown to induce browning of white adipocytes, increase energy consumption, inhibit high-fat diet (HFD)-induced obesity and improve metabolic status. Promoting the activity of brown adipose tissue (BAT) and inducing white adipose tissue (WAT) browning are promising means to increase energy expenditure and improve glucose and lipid metabolism. This review summarizes recent advances in the knowledge of flavonoid compounds and their metabolites. We searched the following databases for all research related to flavonoids and WAT browning published through March 2019: PubMed, MEDLINE, EMBASE, and the Web of Science. All included studies are summarized and listed in Table 1. We summarized the effects of flavonoids on fat metabolism and the specific underlying mechanisms in sub-categories. Flavonoids activated the sympathetic nervous system (SNS), promoted the release of adrenaline and thyroid hormones to increase thermogenesis and induced WAT browning through the AMPK-PGC-1α/Sirt1 and PPAR signalling pathways. Flavonoids may also promote brown preadipocyte differentiation, inhibit apoptosis and produce inflammatory factors in BAT. Flavonoids induced WAT browning and activated BAT to increase energy consumption and non-shivering thermogenesis, thus inhibiting weight gain and preventing metabolic diseases.

The accumulation of macrophages in degenerated discs is a common phenomenon. However, the roles and mechanisms of M2a macrophages in intervertebral disc degeneration (IDD) have not been illuminated. This study investigated the expression of the M2a macrophage marker (CD206) in human and rat intervertebral disc tissues by immunohistochemistry. To explore the roles of M2a macrophages in IDD, nucleus pulposus (NP) cells were co-cultured with M2a macrophages in vitro. To clarify whether the CHI3L1 protein mediates the effect of M2a macrophages on NP cells, siRNA was used to knock down CHI3L1 transcription. To elucidate the underlying mechanisms, NP cells were incubated with recombinant CHI3L1 proteins, then subjected to western blotting analysis of the IL-13Rα2 receptor and MAPK pathway. CD206-positive cells were detected in degenerated human and rat intervertebral disc tissues. Notably, M2a macrophages promoted the expression of catabolism genes (MMP-3 and MMP-9) and suppressed the expression of anabolism genes (aggrecan and collagen II) in NP cells. These effects were abrogated by CHI3L1 knockdown in M2a macrophages. Exposure to recombinant CHI3L1 promoted an extracellular matrix metabolic imbalance in NP cells via the IL-13Rα2 receptor, along with activation of the ERK and JNK MAPK signaling pathways. This study elucidated the roles of M2a macrophages in IDD and identified potential mechanisms for these effects.