Browning of white adipose cells by intermediate metabolites: an adaptive mechanism to alleviate redox pressure.
نویسندگان
چکیده
The presence of brown adipose tissue (BAT) in human adults opens attractive perspectives to treat metabolic disorders. Indeed, BAT dissipates energy as heat via uncoupling protein (UCP)1. Brown adipocytes are located in specific deposits or can emerge among white fat through the so-called browning process. Although numerous inducers have been shown to drive this process, no study has investigated whether it could be controlled by specific metabolites. Here, we show that lactate, an important metabolic intermediate, induces browning of murine white adipose cells with expression of functional UCP1. Lactate-induced browning also occurs in human cells and in vivo. Lactate controls Ucp1 expression independently of hypoxia-inducible factor-1α and PPARα pathways but requires active PPARγ signaling. We demonstrate that the lactate effect on Ucp1 is mediated by intracellular redox modifications as a result of lactate transport through monocarboxylate transporters. Further, the ketone body β-hydroxybutyrate, another metabolite that impacts redox state, is also a strong browning inducer. Because this redox-dependent increase in Ucp1 expression promotes an oxidative phenotype with mitochondria, browning appears as an adaptive mechanism to alleviate redox pressure. Our findings open new perspectives for the control of adipose tissue browning and its physiological relevance.
منابع مشابه
A New Role for Browning as a Redox and Stress Adaptive Mechanism?
The worldwide epidemic of obesity and metabolic disorders is focusing the attention of the scientific community on white adipose tissue (WAT) and its biology. This tissue is characterized not only by its capability to change in size and shape but also by its heterogeneity and versatility. WAT can be converted into brown fat-like tissue according to different physiological and pathophysiological...
متن کاملO-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat
Induction of beige cells causes the browning of white fat and improves energy metabolism. However, the central mechanism that controls adipose tissue browning and its physiological relevance are largely unknown. Here, we demonstrate that fasting and chemical-genetic activation of orexigenic AgRP neurons in the hypothalamus suppress the browning of white fat. O-linked β-N-acetylglucosamine (O-Gl...
متن کاملThe Role of Inflammation and Changes of Adipose Tissue-Resident Immune Cells in Increasing the Risk of Cancer: A Narrative Review
The incidence of obesity, as a major health problem, has increased significantly over the past decades. This condition is associated with an increased risk of cancers, type 2 diabetes, and cardiovascular diseases. The current study aimed to investigate the effects of inflammation and changes of adipose tissue-resident immune cells on increasing the risk of cancer in obese individuals. In obesit...
متن کاملArtepillin C, a Typical Brazilian Propolis-Derived Component, Induces Brown-Like Adipocyte Formation in C3H10T1/2 Cells, Primary Inguinal White Adipose Tissue-Derived Adipocytes, and Mice
Induction of brown-like adipocytes (beige/brite cells) in white adipose tissue (WAT) suggests a new approach for preventing and treating obesity via induction of thermogenesis associated with uncoupling protein 1 (UCP1). However, whether diet-derived factors can directly induce browning of white adipocytes has not been well established. In addition, the underlying mechanism of induction of brow...
متن کاملThe effect of cerebrospinal fluid-derived exosomes on neural differentiation of adipose mesenchymal stem cells in alginate hydrogel scaffold
Nowadays, researchers have made extensive efforts to find new treatments for nerve damage. Meanwhile, the role of exosomes in cell-cell communication is considered to be a new mechanism. Exosomes can act as suitable differentiating agents. The aim of this study was to investigate the differentiating effect of cerebrospinal fluid-derived exosomes on adipose mesenchymal stem cells in alginate hyd...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Diabetes
دوره 63 10 شماره
صفحات -
تاریخ انتشار 2014