The role of novel adipokines and adipose-derived extracellular vesicles (ADEVs): Connections and interactions in liver diseases.

Adipose tissues (AT) are an important endocrine organ that secretes various functional adipokines, peptides, non-coding RNAs, and acts on AT themselves or other distant tissues or organs through autocrine, paracrine, or endocrine manners. An accumulating body of evidence has suggested that many adipokines play an important role in liver metabolism. Besides the traditional adipokines such as adiponectin and leptin, many novel adipokines have recently been identified to have regulatory effects on the liver. Additionally, AT can produce extracellular vesicles (EVs) that act on peripheral tissues. However, under pathological conditions, such as obesity and diabetes, dysregulation of adipokines is associated with functional changes in AT, which may cause liver diseases. In this review, we focus on the newly discovered adipokines and EVs secreted by AT and highlight their actions on the liver under the context of obesity, nonalcoholic fatty liver diseases (NAFLD), and some other liver diseases. Clarifying the action of adipokines and adipose tissue-derived EVs on the liver would help to identify novel therapeutic targets or biomarkers for metabolic diseases.

Metformin plus L-carnitine enhances brown/beige adipose tissue activity via Nrf2/HO-1 signaling to reduce lipid accumulation and inflammation in murine obesity.

This study investigated how Metformin (Met) combined with L-carnitine (L-car) modulates brown adipose tissue (BAT) to affect obesity. High-fat-induced obese rats received daily oral gavage with Met and/or L-car, followed by serum biochemical analysis, histopathological observation on adipose tissues, and immunochemistry test for the abdominal expression of BAT-specific uncoupling protein 1 (UCP1). Mouse-embryonic-fibroblast cells were induced into adipocytes, during which Met plus L-car was added with/without saturated fatty acid (SFA). The role of nuclear factor erythroid 2-related factor 2 (Nrf2) in adipocyte browning was investigated by gene silencing. Mitochondria biogenesis in adipocytes was inspected by Mitotracker staining. Nrf2/heme oxygenase-1 (HO-1)/BAT-related genes/proinflammatory marker expressions in adipose tissues and/or adipocytes were analyzed by Western blot, qRT-PCR, and/or immunofluorescence test. Met or L-car improved metabolic disorders, reduced adipocyte vacuolization and swelling, upregulated levels of BAT-related genes including UCP1 and downregulated proinflammatory marker expressions, and activated the Nrf2/HO-1 pathway in adipose tissues of obese rats. Met and L-car functioned more strongly than alone. In adipocytes, Met plus L-car upregulated BAT-related gene levels and protected against SFA-caused inflammation promotion and mitochondria degeneration, which yet was attenuated by Nrf2 silencing. Met plus L-car enhances BAT activity and white adipose tissue browning via the Nrf2/HO-1 pathway to reduce lipid accumulation and inflammation in obese rats.

Long-term depot specific changes in adipose tissue after treatment of acromegaly.

CONTEXT: Patients with active acromegaly present a decreased adipose tissue (AT) mass, and short-term studies show that treatment leads to AT depot-specific gain. However, it remains unclear if the increase is persistent in the long-term perspective and/or is sex-dependent. DESIGN: To characterize the depot-specific changes of AT after treatment of acromegaly and identify contributing factors. METHODS: Adipose tissue, including visceral (VAT), subcutaneous (SAT), and total (TAT), and android to gynoid ratio (A/G ratio) were measured by dual energy X-ray absorptiometry at diagnosis (n = 62), and after treatment at short-term (median (IQR) 1.9 (1.5-2.3)) and long-term 5.5 (3.9-9.5) years, and correlated to clinical and biochemical measurements. Growth hormone (GH), insulin-like growth factor 1 (IGF-1), glucose and HbA1c levels, gonadal status, and the presence of diabetes mellitus were recorded. Remission status was assessed at the long-term visit (IGF-1/ULN ≤ 1.3). Differences in the temporal course of AT from baseline to short- and long-term follow-up according to sex, diabetes, gonadal, and remission status were evaluated by mixed model analysis, adjusted for age. RESULTS: Despite a stable body mass index, VAT and A/G ratio increased at both time points, whereas SAT mainly increased at short-term, plateauing afterwards (P < .05 for all). Visceral adipose tissue and A/G ratio were higher in men (P = .035 and P < .001), and the A/G ratio increased more than in women (P = .003). Glucose and HbA1c decreased short-term (P < .05) and remained stable at long-term. The increase in AT depots correlated with the decrease of disease activity at long-term. Remission status had no effect on changes in AT mass during follow-up. CONCLUSION: Treatment of acromegaly leads to an increase in AT mass in a depot- and sex-specific manner both at short-term and long-term follow-up. Glucose metabolism improves rapidly after disease control and persists.

Myogenic Differentiation and Immunomodulatory Properties of Rat Adipose-Derived Mesenchymal Stem/Stromal Cells.

The myogenic differentiation potential of MSCs is a key factor in their potential use as a cell source for muscle tissue repair and regeneration. Additionally, evaluating the immunomodulatory properties of MSCs is important to highlight their potential for regulating inflammation and supporting tissue regeneration. Given the limited literature on muscle differentiation potential and immunomodulatory properties, this study aims to characterize rat ADP MSCs for treating muscle disease. We isolated MSCs from adipose tissues around the periscapular region of the rats. We used a monoculture method for the myogenic differentiation and modified the myogenic induction medium by supplementing it with the growth factors FGF, HGF, and IGF. In rat ADP MSCs, expression of the MSC-specific marker, CD90, was 87.7%, while CD44 was 42.8%. For genes involved in immunomodulation, IGF1 and TGFB1 were highly expressed, while IL6 was poorly expressed. In addition to their trilineage differentiation potential, ADP MSCs exhibited the capacity to differentiate into myogenic cell lines, as evidenced by changes in cell morphology, leading to elongated and aligned structures and the expression of the MyoD and MYOG antibodies. The study found that ADP MSCs show great clinical promise for muscle regeneration.

Characterization of Rabbit Mesenchymal Stem/Stromal Cells after Cryopreservation.

Adipose tissues (ADPs) are an alternative source for mesenchymal stem/stromal cells (MSCs), given that conventional bone marrow (BM) collection is painful and yields limited cell numbers. As the need for easily accessible MSCs grows, cryopreservation's role in regenerative medicine is becoming increasingly vital. However, limited research exists on the characteristics and functional properties of rabbit-derived MSCs from various anatomical sources before and after cryopreservation. We examined the effects of cryopreservation using Bambanker. We found that cryopreservation did not adversely affect the morphology, viability, and adipogenic or chondrogenic differentiation abilities of ADP MSCs or BM MSCs. However, there was a notable drop in the proliferation rate and osteogenic differentiation capability of BM MSCs post-cryopreservation. Additionally, after cryopreservation, the surface marker gene expression of CD90 was not evident in ADP MSCs. As for markers, ADIPOQ can serve as an adipogenic marker for ADP MSCs. ACAN and CNMD can act as chondrogenic markers, but these two markers are not as effective post-cryopreservation on ADP MSCs, and osteogenic markers could not be validated. The study highlights that compared to BM MSCs, ADP MSCs retained a higher viability, proliferation rate, and differentiation potential after cryopreservation. As such, in clinical MSC use, we must consider changes in post-cryopreservation cell functions.

The nervous system and adipose tissues: a tale of dialogues.

White, beige, and brown adipose tissues play a crucial role in maintaining energy homeostasis. Due to the heterogeneous and diffuse nature of fat pads, this balance requires a fine and coordinated control of many actors and therefore permanent dialogues between these tissues and the central nervous system. For about two decades, many studies have been devoted to describe the neuro-anatomical and functional complexity involved to ensure this dialogue. Thus, if it is now clearly demonstrated that there is an efferent sympathetic innervation of different fat depots controlling plasticity as well as metabolic functions of the fat pad, the crucial role of sensory innervation capable of detecting local signals informing the central nervous system of the metabolic state of the relevant pads is much more recent. The purpose of this review is to provide the current state of knowledge on this subject.

Adipose tissue­derived extracellular vesicles: Systemic messengers in health and disease (Review).

Adipose tissue (AT) is a complicated metabolic organ consisting of a heterogeneous population of cells that exert wide­ranging effects on the regulation of systemic metabolism and in maintaining metabolic homeostasis. Various obesity­related complications are associated with the development of dysfunctional AT. As an essential transmitter of intercellular information, extracellular vesicles (EVs) have recently been recognized as crucial in regulating multiple physiological functions. AT­derived extracellular vesicles (ADEVs) have been shown to facilitate cellular communication both inside and between ATs and other peripheral organs. Here, the role of EVs released from ATs in the homeostasis of metabolic and cardiovascular diseases, cancer, and neurological disorders by delivering lipids, proteins, and nucleic acids between different cells is summarized. Furthermore, the differences in the sources of ADEVs, such as adipocytes, AT macrophages, AT­derived stem cells, and AT­derived mesenchymal stem cells, are also discussed. This review may provide valuable information for the potential application of ADEVs in metabolic syndrome, cardiovascular diseases, cancer, and neurological disorders.

3D Elastomeric Stent Functionalized with Antioxidative and Perivascular Tissue Regenerative Activities Ameliorated PVT Deprivation-Induced Vein Graft Failure.

Clinically, arterial injuries are always accompanied with perivascular tissue damage, which may contribute to high failure rate of vein grafts due to intimal hyperplasia and acute thrombosis. In this study, a "perivascular tissue (PVT) deprivation" animal model is constructed to mimic clinical scenarios and identify the contribution of arterial PVT to the success of vein grafts. Proteomics analysis suggests that depriving PVT may exacerbate reactive oxygen species (ROS)-induced endothelial apoptosis by up-regulating inflammation response and oxidative stress. Locally administering metformin on vein grafts through 3D-printed external stent (PGS-PCL) shows antioxidative and anti-inflammatory properties to protect cells from ROS invasion, thereafter decreasing acute thrombosis. Moreover, metformin induce rapid regeneration of perivascular adipose tissue in recipient regions, which improves patency by inhibiting intimal hyperplasia. Proteomics, western blot, and in vitro blocking tests reveal that metformin resists endothelial apoptosis through AMPK/mTOR and NFκB signaling pathways. To conclude, PVT deprivation exacerbates inflammatory response and oxidative stress in vein grafts bridging arterial circulation. Metformin-loaded stent ameliorates "PVT damage" related vein graft failure, and enhances patency of through resisting endothelial apoptosis and regenerating arterial PVAT, offering a promising avenue to improve the success of vein grafts in clinic.

Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in adipose tissue of women from Grand Tunis and their association with demographic factors and dietary habits.

Dichlorodiphenyl trichloroethane and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB) and polychloronated biphenyls (PCBs) were measured in 25 woman adipose tissues collected in 2016 from Grand Tunis, Tunisia. p,p'-DDE, p,p'-DDT, HCB and ß-HCH were the dominant organochlorine pesticides (OCPs) in decreasing order in all samples. The total OCP levels varied from 79 to 343 ng g-1 lipid with a median value of 189 ng g-1 lipid and DDTs contributed approximately 88% to sum OCP. The ratio of p,p'-DDT/p,p'-DDE across all samples is below one, which suggests mainly historic exposure but may indicate some recent exposure to the banned pesticide. The median concentration of PCBs was 109 ng g-1 lipid and ranged between 27 and 204 ng g-1 lipid. PCB-153, PCB-180, PCB-138 and PCB-170 were the most abundant congeners, which contributed about 78% of the total PCBs. Spearman analysis showed that dominant organochlorine compounds (OCs) are highly positive correlated except for PCB-28/31, indicating that women from Tunis are exposed via similar routes. Inhalation exposure could be a possible pathway for the uptake of the less chlorinated congeners. We found positive and statistically significant association with subjects age for HCB (r = 0.517; p = 0.009) and PCBs (r = 0.65; p = 0.001) levels and a weak age-dependent accumulation was found for HCHs (r = 0.375; p = 0.065) and DDTs (r = 0.388; p = 0.056). The concentrations of OC subgroups were not associated with BMI, parity and residence. No association was observed between fish, red/white meat, milk and dairy products consumption and levels of HCB, HCHs and PCBs. DDTs levels were significantly correlated only with milk (p = 0.048) and milk products (p = 0.047) intake.

"Turning up the heat": role of neurotrophic batokines in the postnatal maturation and remodeling of brown adipose tissue in deer mice.

Activation of brown adipose tissue (BAT) thermogenesis impacts energy balance and must be tightly regulated. Several neurotrophic factors, expressed in BAT of adult laboratory rodents, have been implicated in remodeling the sympathetic neural network to enhance thermogenesis [e.g., nerve growth factor (NGF), neuregulin-4 (NRG4), and S100b]. Here, we compare, to our knowledge, for the first time, the relative roles of three neurotrophic "batokines" in establishing/remodeling innervation during postnatal development and adult cold stress. We used laboratory-reared Peromyscus maniculatus, which rely heavily on BAT-based thermogenesis for survival in the wild, beginning between postnatal days (P) 8 and 10. BAT sympathetic innervation was enhanced from P6 to P10, and exogenous NGF, NRG4, and S100b stimulated neurite outgrowth from P6 sympathetic neurons. Endogenous BAT protein stores and/or gene expression of NRG4, S100b, and calsyntenin-3ß (which may regulate S100b secretion) remained high and constant during development. However, endogenous NGF was low and ngf mRNA was undetectable. Conditioned media (CM) from cultured P10 BAT slices stimulated neurite outgrowth from sympathetic neurons in vitro, which was inhibited by antibodies against all three growth factors. P10 CM had significant amounts of secreted NRG4 and S100b protein, but not NGF. By contrast, BAT slices from cold-acclimated adults released significant amounts of all three factors relative to thermoneutral controls. These data suggest that although neurotrophic batokines regulate sympathetic innervation in vivo, their relative contributions differ depending on the life stage. They also provide novel insights into the regulation of BAT remodeling and BAT's secretory role, both of which are critical to our understanding of mammalian energy homeostasis.NEW & NOTEWORTHY In altricial Peromyscus mice, the developmental shift to endothermy accompanies the establishment of the brown adipose tissue sympathetic neural network. Cultured slices of neonatal BAT secreted high quantities of two predicted neurotrophic batokines: S100b and neuregulin-4, but surprisingly low levels of the classic neurotrophic factor, NGF. Despite low NGF, neonatal BAT-conditioned media was highly neurotrophic. Cold-exposed adults use all three factors to dramatically remodel BAT, suggesting that BAT-neuron communication is life-stage dependent.

Human iPSC-Derived Proinflammatory Macrophages cause Insulin Resistance in an Isogenic White Adipose Tissue Microphysiological System.

Chronic white adipose tissue (WAT) inflammation has been recognized as a critical early event in the pathogenesis of obesity-related disorders. This process is characterized by the increased residency of proinflammatory M1 macrophages in WAT. However, the lack of an isogenic human macrophage-adipocyte model has limited biological studies and drug discovery efforts, highlighting the need for human stem cell-based approaches. Here, human induced pluripotent stem cell (iPSC) derived macrophages (iMACs) and adipocytes (iADIPOs) are cocultured in a microphysiological system (MPS). iMACs migrate toward and infiltrate into the 3D iADIPOs cluster to form crown-like structures (CLSs)-like morphology around damaged iADIPOs, recreating classic histological features of WAT inflammation seen in obesity. Significantly more CLS-like morphologies formed in aged and palmitic acid-treated iMAC-iADIPO-MPS, showing the ability to mimic inflammatory severity. Importantly, M1 (proinflammatory) but not M2 (tissue repair) iMACs induced insulin resistance and dysregulated lipolysis in iADIPOs. Both RNAseq and cytokines analyses revealed a reciprocal proinflammatory loop in the interactions of M1 iMACs and iADIPOs. This iMAC-iADIPO-MPS thus successfully recreates pathological conditions of chronically inflamed human WAT, opening a door to study the dynamic inflammatory progression and identify clinically relevant therapies.

Development and validation of a nonenhanced CT based radiomics model to detect brown adipose tissue.

Purpose: It has been reported that brown adipose tissue (BAT) has a protective effect regarding cardiovascular disease. Positron emission tomography-computed tomography (PET-CT) is the reference method for detecting active BAT; however, it is not feasible to screen for BAT due to the required radionuclides and high-cost. The purpose of this study is to develop and validate a nonenhanced CT based radiomics model to detect BAT and to explore the relationship between CT radiomics derived BAT and cardiovascular calcification. Patients and methods: 146 patients undergoing 18F-FDG PET-CT were retrospectively included from two centers for model development (n = 86) and external validation (n = 60). The data for the model development were randomly divided into a training cohort and an internal validation cohort with a 7:3 ratio, while the external validation data were divided 1:1 into a propensity score matching (PSM) cohort and a randomly sex matched cohort. Radiomics features of BAT and non-BAT depots were extracted from regions of interest (ROI) on nonenhanced CT corresponding to PET studies. Inter-class correlation coefficient (ICC) and Pearson's correlation analysis were performed to select radiomics features with high consistency. Next, least absolute shrinkage and selection operator (LASSO) with linear regression model was used to select radiomics features for model construction. Support vector machine (SVM) was used to develop the model and a radiomics score (RS) was calculated for each depot. The diagnostic performance of the radiomics model was evaluated both on a per-depot and per-patient basis by calculating the area under the receiver operating characteristic curve (AUROC). We further divided patients into BAT-RS group and non-BAT-RS group based on radiomics score and compared their cardiovascular calcification by calculating calcium volume and score. Results: A total of 22 radiomics features were selected for model construction. On a per-depot basis, the AUROCs were 0.87 (95% CI: 0.83-0.9), 0.85 (95% CI: 0.79-0.90), 0.72 (95% CI: 0.67-0.77) and 0.74 (95% CI: 0.69-0.79) for detecting BAT in the training, internal validation, external validation 1 and external validation 2 cohorts, respectively. On a per-patient basis, the radiomics model had high AUROCs of 0.91 (95% CI: 0.84-0.98), 0.77 (95% CI: 0.61-0.92) and 0.85 (95% CI: 0.72-0.98) in the training, external validation 1 and external validation 2 cohorts, respectively. When grouping based on the radiomics model, the BAT-RS group had lower odds of coronary artery calcium (CAC) and thoracic aorta calcium (TAC) compared with the non-BAT-RS group (CAC: 2.8% vs. 20.3%, p = 0.001; TAC: 19.4% vs. 39.2%, p = 0.009). The BAT-RS group had less CAC volume (4.1 ± 4.0 mm3 vs. 147.4 ± 274.3 mm3; p = 0.001), CAC score (2.8 ± 3.0 vs. 169.1 ± 311.5; p = 0.001), TAC volume (301.4 ± 450.2 mm3 vs. 635.3 ± 1100.7 mm3; p = 0.007) and TAC score (496.2 ± 132.6 vs. 749.2 ± 1297.3; p = 0.007) than the non-BAT-RS group. Conclusion: We developed and validated a nonenhanced CT based reliable radiomics model for detecting BAT with PET-CT findings as reference standard. Radiomics signatures from nonenhanced CT can reliably detect BAT and have promising potential to be used in routine clinical settings. Importantly, our study showed that patients with BAT had less cardiovascular calcification.

Adipose Tissue Remodeling in Obesity: An Overview of the Actions of Thyroid Hormones and Their Derivatives.

Metabolic syndrome and obesity have become important health issues of epidemic proportions and are often the cause of related pathologies such as type 2 diabetes (T2DM), hypertension, and cardiovascular disease. Adipose tissues (ATs) are dynamic tissues that play crucial physiological roles in maintaining health and homeostasis. An ample body of evidence indicates that in some pathophysiological conditions, the aberrant remodeling of adipose tissue may provoke dysregulation in the production of various adipocytokines and metabolites, thus leading to disorders in metabolic organs. Thyroid hormones (THs) and some of their derivatives, such as 3,5-diiodo-l-thyronine (T2), exert numerous functions in a variety of tissues, including adipose tissues. It is known that they can improve serum lipid profiles and reduce fat accumulation. The thyroid hormone acts on the brown and/or white adipose tissues to induce uncoupled respiration through the induction of the uncoupling protein 1 (UCP1) to generate heat. Multitudinous investigations suggest that 3,3',5-triiodothyronine (T3) induces the recruitment of brown adipocytes in white adipose depots, causing the activation of a process known as "browning". Moreover, in vivo studies on adipose tissues show that T2, in addition to activating brown adipose tissue (BAT) thermogenesis, may further promote the browning of white adipose tissue (WAT), and affect adipocyte morphology, tissue vascularization, and the adipose inflammatory state in rats receiving a high-fat diet (HFD). In this review, we summarize the mechanism by which THs and thyroid hormone derivatives mediate adipose tissue activity and remodeling, thus providing noteworthy perspectives on their efficacy as therapeutic agents to counteract such morbidities as obesity, hypercholesterolemia, hypertriglyceridemia, and insulin resistance.

Protective effect of rosmarinic acid-rich extract from Trichodesma khasianum Clarke against microbiota dysbiosis in high-fat diet-fed obese mice.

Hypertrophy of adipose tissues and dysbiosis are hallmarks of obesity. Although drugs are applied for obesity treatment, side effects limit their use. The anti-obesity capacity of rosmarinic acid (RA) has been documented. Trichodesma khasianum Clarke is an edible RA-rich plant grown in Taiwan. Our previous study found that an 80 % ethanol extract of T. khasianum Clarke leaves (80EETC) ameliorates gastric mucosal damage through its anti-inflammatory, antioxidant, and microbiota modulation abilities. However, the anti-obesity effect of 80EETC remains unclear. Therefore, the objective of this study was to explore the protective effects of low-dose 80EETC (125 mg/kg b.w., 80EETCL) or high-dose 80EETC (250 mg/kg b.w., 80EETCH) on obesity development through gut microbiota modulation in high-fat diet (HFD)-induced C57BL/6 mice. The results showed a high RA content (89.2 ± 7.4 mg/g) in 80EETC. 80EETC administration significantly decreased body weight, body fat ratio, serum lipid levels (TC, TG, and LDL-C), adipose tissue accumulation, malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α) in HFD-fed mice. Furthermore, supplementation with 80EETC reduced the Firmicutes/Bacteroidetes ratio and enhanced the relative abundance of gut microbiota (p_Bacteroidetes, f_Lactobacillus, f_Muribaculaceae, f_Prevotellaceae, g_Lactobacillus, g_Prevotellaceae_NK3B31_group, g_Ruminococcaceae_UCG-013, and g_Ruminococcaceae_UCG-014), which negatively correlated with obesity-related factors such as body weight, energy intake, fat accumulation in adipose tissue, TC, TG, LDL, and MDA. In conclusion, RA-rich 80EETC had a protective effect against obesity development and it has potential in healthy food applications.

Microbe-Derived Antioxidants Alleviate Liver and Adipose Tissue Lipid Disorders and Metabolic Inflammation Induced by High Fat Diet in Mice.

Obesity induces lipodystrophy and metabolic inflammation. Microbe-derived antioxidants (MA) are novel small-molecule nutrients obtained from microbial fermentation, and have anti-oxidation, lipid-lowering and anti-inflammatory effects. Whether MA can regulate obesity-induced lipodystrophy and metabolic inflammation has not yet been investigated. The aim of this study was to investigate the effects of MA on oxidative stress, lipid disorders, and metabolic inflammation in liver and epididymal adipose tissues (EAT) of mice fed with a high-fat diet (HFD). Results showed that MA was able to reverse the HFD-induced increase in body weight, body fat rate and Lee's index in mice; reduce the fat content in serum, liver and EAT; and regulate the INS, LEP and resistin adipokines as well as free fatty acids to their normal levels. MA also reduced de novo synthesis of fat in the liver and EAT and promoted gene expression for lipolysis, fatty acid transport and ß-oxidation. MA decreased TNF-α and MCP1 content in serum, elevated SOD activity in liver and EAT, induced macrophage polarization toward the M2 type, inhibited the NLRP3 pathway, increased gene expression of the anti-inflammatory factors IL-4 and IL-13 and suppressed gene expression of the pro-inflammatory factors IL-6, TNF-α and MCP1, thereby attenuating oxidative stress and inflammation induced by HFD. In conclusion, MA can effectively reduce HFD-induced weight gain and alleviate obesity-induced oxidative stress, lipid disorders and metabolic inflammation in the liver and EAT, indicating that MA shows great promise as a functional food.

Redox Biology in Adipose Tissue Physiology and Obesity.

Reactive oxygen species (ROS), a by-product of mitochondrial oxidative phosphorylation and cellular metabolism, is vital for cellular survival, proliferation, damage, and senescence. In recent years, studies have shown that ROS levels and redox status in adipose tissue are strongly associated with obesity and metabolic diseases. Although it was previously considered that excessive production of ROS and impairment of antioxidant capability leads to oxidative stress and potentially contributes to increased adiposity, it has become increasingly evident that an adequate amount of ROS is vital for adipocyte differentiation and thermogenesis. In this review, by providing a systematic overview of the recent understanding of the key factors of redox systems, endogenous mechanisms for redox homeostasis, advanced techniques for dynamic redox monitoring, as well as exogenous stimuli for redox production in adipose tissues and obesity, the importance of redox biology in metabolic health is emphasized.

Brown Adipose Tissue-A Translational Perspective.

Brown adipose tissue (BAT) displays the unique capacity to generate heat through uncoupled oxidative phosphorylation that makes it a very attractive therapeutic target for cardiometabolic diseases. Here, we review BAT cellular metabolism, its regulation by the central nervous and endocrine systems and circulating metabolites, the plausible roles of this tissue in human thermoregulation, energy balance, and cardiometabolic disorders, and the current knowledge on its pharmacological stimulation in humans. The current definition and measurement of BAT in human studies relies almost exclusively on BAT glucose uptake from positron emission tomography with 18F-fluorodeoxiglucose, which can be dissociated from BAT thermogenic activity, as for example in insulin-resistant states. The most important energy substrate for BAT thermogenesis is its intracellular fatty acid content mobilized from sympathetic stimulation of intracellular triglyceride lipolysis. This lipolytic BAT response is intertwined with that of white adipose (WAT) and other metabolic tissues, and cannot be independently stimulated with the drugs tested thus far. BAT is an interesting and biologically plausible target that has yet to be fully and selectively activated to increase the body's thermogenic response and shift energy balance. The field of human BAT research is in need of methods able to directly, specifically, and reliably measure BAT thermogenic capacity while also tracking the related thermogenic responses in WAT and other tissues. Until this is achieved, uncertainty will remain about the role played by this fascinating tissue in human cardiometabolic diseases.

Adipose-Renal Axis in Diabetic Nephropathy.

Long-term diabetes can lead to renal injury known as diabetic nephropathy (DN), which is a major cause of end-stage renal disease (ESRD). However, its pathogenesis has not been well explained. Adipose tissue is recognized as an important energy storage device for the body. Interestingly, many studies have shown that adipose tissue can also act as an endocrine organ by secreting a variety of adipokines to maintain homeostasis. Here, we summarize some of the adipokines that have been identified so far to, more specifically, emphasize their role in DN progression and propose that the "adipose-renal axis" may be a potential target for treating DN.

RNA-Seq revealed the effect of adding different proportions of wheat diet on fat metabolism of Tibetan lamb.

The objective of this study was to evaluate the effect of the level of wheat substitution for corn on the fat metabolism of Tibetan lamb. A total of 90 Tibetan lambs [body weight (BW) of 19.78 ± 2.45 kg] were arranged with three substitution levels of wheat: WC (100 % corn), WL (10 % wheat substitution for corn), and WH (15 % wheat substitution for corn) on a dry matter basis. After the experiment, cry section technology was used to scrutinize the subcutaneous adipose tissue morphology, and genes related to fat metabolism were excavated using high-throughput sequencing technology. According to the study results, fat diameter and fat biovolume of the WL and WH groups were less than the WC group. A total of 506 differentially expressed genes (DEGs) were identified by RNA sequencing (RNA-Seq) technology. Compared with the WC group, 66 DEGs were upregulated and 59 DEGs were downregulated in the WL group, and 179 DEGs were upregulated and 269 DEGs were downregulated in the WH group. The top 20 DEGs were analyzed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway, indicating significant differences in the fat metabolism pathway. Five DEGs were randomly screened for quantitative reverse transcription-polymerase chain reaction (qRT-PCR) verification, and the results were consistent with the RNA-Seq results, which proved the accuracy of sequencing. In summary, with the increase in the proportion of supplemental wheat, the fat cells became smaller, and the genes related to fat decomposition were significantly upregulated.

Association between Retinol-Binding Protein 4 Levels and Preeclampsia: A Systematic Review and Meta-Analysis.

Retinol-binding protein 4 (RBP4) is claimed to be associated with the development of preeclampsia, yet the reports are inconclusive. This systematic review and meta-analysis aimed to assess the association between RBP4 levels and preeclampsia. The PubMed, Google Scholar and ScienceDirect databases were searched for studies that investigated RBP4 levels in preeclampsia patients and compared them with normal controls. The meta-analysis was conducted by calculating the standardized mean difference (SMD) of RBP4 between cases and controls. The meta package with the R software was used to perform all statistical analysis. A total of 13 studies, comprising 569 cases and 1411 controls, met the inclusion criteria and were thus included in the meta-analysis. According to the random effect model, the SMD of RBP4 was significantly higher in women with preeclampsia compared with normal controls [SMD of RBP4: 0.55 ng/mL; 95% CI (0.06; 1.05); p = 0.028; I2 = 89%]. Likewise, the stratified meta-analysis showed the same pattern in the studies which measured RBP4 levels in the third trimester, as well as in the studies that investigated severe preeclampsia. Meta-regression did not identify any factor that significantly affected the overall estimate. There was no evidence of reporting bias (Egger's test; t = 0.43; p = 0.587). This meta-analysis with high heterogeneity showed that higher levels of RBP4 were associated with preeclampsia risk. More longitudinal studies spanning the three trimester periods are needed to clarify the association of RBP4 and its dynamics in preeclampsia cases throughout pregnancy.