Consumption of interesterified palm oil leads inflammation of white adipose tissue and triggers metabolic disturbances in mice on a high-fat diet.

Growing obesity is linked to shifts in dietary patterns, particularly the increased intake of ultra-processed high-fat foods. This study aimed to evaluate the effects of interesterified palm oil consumption on glucose homeostasis, adipose tissue remodeling, and hepatic lipogenesis in C57BL/6 mice fed a high-fat diet. Sixty C57BL/6 mice were divided into four groups (n = 15): the control group (C) fed a standard diet (4% soybean oil), the high-fat group (HF) (23.8% lard), the high palm oil fat group (HFP) (23.8% palm oil), and the high interesterified palm fat group (HFI) (23.8% interesterified palm oil) for 8 weeks (all groups received 50% energy from lipids). The HFI group exhibited higher body mass than the HF group (+ 11%, P < 0.05), which was attributed to an increased percentage of fat mass. Plasma concentrations of IL-6, insulin, and HOMA-IR were also elevated in the HFI group. Both the HFP and HFI groups showed hypertrophied adipocytes and pancreatic islets, increased alpha and beta cell masses, hepatic steatosis, low expression of genes related to beta-oxidation, and upregulated lipogenesis. In conclusion, the consumption of interesterified palm oil alters inflammatory and glucose profiles.

Exercise enhances hepatic mitochondrial structure and function while preventing endoplasmic reticulum stress and metabolic dysfunction-associated steatotic liver disease in mice fed a high-fat diet.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has attracted increasing attention from the scientific community because of its severe but silent progression and the lack of specific treatment. Glucolipotoxicity triggers endoplasmic reticulum (ER) stress with decreased beta-oxidation and enhanced lipogenesis, promoting the onset of MASLD, whereas regular physical exercise can prevent MASLD by preserving ER and mitochondrial function. Thus, the hypothesis of this study was that high-intensity interval training (HIIT) could prevent the development of MASLD in high-fat (HF)-fed C57BL/6J mice by maintaining insulin sensitivity, preventing ER stress, and promoting beta-oxidation. Forty male C57BL/6J mice (3 months old) comprised 4 experimental groups: the control (C) diet group, the C diet + HIIT (C-HIIT) group, the HF diet group, and the HF diet + HIIT (HF-HIIT) group. HIIT sessions lasted 12 minutes and were performed 3 times weekly by trained mice. The diet and exercise protocols lasted for 10 weeks. The HIIT protocol prevented weight gain and maintained insulin sensitivity in the HF-HIIT group. A chronic HF diet increased ER stress-related gene and protein expression, but HIIT helped to maintain ER homeostasis, preserve mitochondrial ultrastructure, and maximize beta-oxidation. The increased sirtuin-1/peroxisome proliferator-activated receptor-gamma coactivator 1-alpha expression implies that HIIT enhanced mitochondrial biogenesis and yielded adequate mitochondrial dynamics. High hepatic fibronectin type III domain containing 5/irisin agreed with the antilipogenic and anti-inflammatory effects observed in the HF-HIIT group, reinforcing the antisteatotic effects of HIIT. Thus, we confirmed that practicing HIIT 3 times per week maintained insulin sensitivity, prevented ER stress, and enhanced hepatic beta-oxidation, impeding MASLD development in this mouse model even when consuming high energy intake from saturated fatty acids.

Revisiting pancreatic islet isolation in murine models: A practical and effective technical protocol.

The endocrine pancreas is composed of clusters of cell groups called pancreatic islets. These cells are responsible for the synthesis and secretion of hormones crucial for glycemic homeostasis, such as insulin and glucagon. Therefore, these cells were the targets of many studies. One method to study and/or understand endocrine pancreatic physiology is the isolation of these islets and stimulation of hormone production using different concentrations of glucose, agonists, and/or antagonists of specific secretagogues and mimicking the stimulation of hormonal synthesis and secretion. Many researchers studied pancreatic physiology in murine models due to their ease of maintenance and rapid development. However, the isolation of pancreatic islets involves meticulous processes that may vary between rodent species. The present study describes a simple and effective technical protocol for isolating intact islets from mice and rats for use as a practical guide for researchers. The method involves digestion of the acinar parenchyma by intraductal collagenase. Isolated islets are suitable for in vitro endocrine secretion analyses, microscopy techniques, and biochemical analyses.

Time-dependent impact of a high-fat diet on the intestinal barrier of male mice.

BACKGROUND: Excessive saturated fat intake compromises the integrity of the intestinal mucosa, leading to low-grade inflammation, impaired mucosal integrity, and increased intestinal permeability, resulting in the migration of lipopolysaccharide (LPS) to other tissues. AIM: To evaluate the chronic effects (at 10 and 16 wk) of a high-fat diet (HFD) (with 50% energy as fat) on the phylogenetic gut microbiota distribution and intestinal barrier structure and protection in C57BL/6 mice. METHODS: Forty adult male mice were divided into four nutritional groups, where the letters refer to the type of diet (control and HFD or HF) and the numbers refer to the period (in weeks) of diet administration: Control diet for 10 wk, HFD for 10 wk, control diet for 16 wk, and HFD for 16 wk. After sacrifice, biochemical, molecular, and stereological analyses were performed. RESULTS: The HF groups were overweight, had gut dysbiosis, had a progressive decrease in occludin immunostaining, and had increased LPS concentrations. Dietary progression reduced the number of goblet cells per large intestine area and Mucin2 expression in the HF16 group, consistent with a completely disarranged intestinal ultrastructure after 16 wk of HFD intake. CONCLUSION: Chronic HFD intake causes overweight, gut dysbiosis, and morphological and functional alterations of the intestinal barrier after 10 or 16 wk. Time-dependent reductions in goblet cell numerical density and mucus production have emerged as targets for countering obesity-driven intestinal damage.

Anti-steatotic effects of PPAR-alpha and gamma involve gut-liver axis modulation in high-fat diet-fed mice.

AIM: To evaluate the effects of PPARα and PPARγ activation (alone or in combination) on the gut-liver axis, emphasizing the integrity of the intestinal barrier and hepatic steatosis in mice fed a high saturated fat diet. METHODS: Male C57BL/6J were fed a control diet (C) or a high-fat diet (HF) for ten weeks. Then, a four-week treatment started: HF-α (WY14643), HF-γ (low-dose pioglitazone), and HF-αγ (combination). RESULTS: The HF caused overweight, insulin resistance, impaired gut-liver axis, and marked hepatic steatosis. Treatments reduced body mass, improved glucose homeostasis, and restored the gut microbiota diversity and intestinal barrier gene expression. Treatments also lowered the plasma lipopolysaccharide concentrations and favored beta-oxidation genes, reducing macrophage infiltration and steatosis in the liver. CONCLUSION: Treatment with PPAR agonists modulated the gut microbiota and rescued the integrity of the intestinal barrier, alleviating hepatic steatosis. These results show that these agonists can contribute to metabolic-associated fatty liver disease treatment.

Brown Adipose Tissue, Batokines, and Bioactive Compounds in Foods: An Update.

The discovery of metabolically active brown adipose tissue (BAT) in human adults and the worldwide increase in obesity and obesity-related chronic noncommunicable diseases (NCDs) has made BAT a therapeutic target in the last two decades. The potential of BAT to oxidize fatty acids rapidly and increase energy expenditure inversely correlates with adiposity, insulin and glucose resistance, and cardiovascular and metabolic diseases. Currently, BAT is recognized by a new molecular signature; several BAT-derived molecules that act positively on target tissues have been identified and collectively called batokines. Bioactive compounds present in foods are endowed with thermogenic properties that increase BAT activation signaling. Understanding the mechanisms that lead to BAT activation and the batokines secreted by it within the thermogenic state is fundamental for its recruitment and management of obesity and NCDs. This review contributes to recent updates on the morphophysiology of BAT, its endocrine role in obesity, and the main bioactive compounds present in foods involved in classical and nonclassical thermogenic pathways activation.

An Intestinal FXR Agonist Mitigates Dysbiosis, Intestinal Tight Junctions, and Inflammation in High-Fat Diet-Fed Mice.

SCOPE: To analyze the effects of fexaramine (FEX), as an intestinal FXR agonist, on the modulation of the intestinal microbiota and ileum of mice fed a high-fat (HF) diet. METHODS AND RESULTS: Three-month-old C57Bl/6 male mice are divided into two groups and received a control (C, 10% of energy from lipids) or HF (50% of energy from lipids) diet for 12 weeks. They are subdivided into the C, C + FEX, HF, and HF + FEX groups. FEX is administered (FEX-5 mg kg-1 ) via orogastric gavage for three weeks. Body mass (BM), glucose metabolism, qPCR 16S rRNA gene expression, and ileum gene expression, bile acids (BAs), tight junctions (TJs), and incretin are analyzed. FEX reduces BM and glucose intolerance, reduces plasma lipid concentrations and the Firmicutes/Bacteroidetes ratio, increases the Lactobacillus sp. and Prevotella sp. abundance, and reduces the Escherichia coli abundance. Consequently, the ileal gene expression of Fxr-Fgf15, Tgr5-Glp1, and Cldn-Ocldn-Zo1 is increased, and Tlr4-Il6-Il1beta is decreased. CONCLUSION: FEX stimulates intestinal FXR and improves dysbiosis, intestinal TJs, and the release of incretins, mitigating glucose intolerance and BM increases induced by an HF diet. However, FEX results in glucose intolerance, insulin resistance, and reduces intestinal TJs in a control group, thus demonstrating limitations to this dietary model.

PPARα/γ synergism activates UCP1-dependent and -independent thermogenesis and improves mitochondrial dynamics in the beige adipocytes of high-fat fed mice.

OBJECTIVE: The aim of this study was to investigate the role of peroxisome proliferator-activated receptor (PPAR) activation (single PPARα or PPARγ, and dual PPARα/γ) on UCP1-dependent and -independent thermogenic pathways and mitochondrial metabolism in the subcutaneous white adipose tissue of mice fed a high-fat diet. METHODS: Male C57BL/6 mice received either a control diet (10% lipids) or a high-fat diet (HF; 50% lipids) for 12 wk. The HF group was divided to receive the treatments for 4 wk: HFγ (pioglitazone, 10 mg/kg), HFα (WY-14643, 3.5 mg/kg), and HFα/γ (tesaglitazar, 4 mg/kg). RESULTS: The HF group was overweight, insulin resistant, and had subcutaneous white adipocyte dysfunction. Treatment with PPARα and PPARα/γ reduced body mass, mitigated insulin resistance, and induced browning with increased UCP1-dependent and -independent thermogenesis activation and improved mitochondrial metabolism to support the beige adipocyte phenotype. CONCLUSION: PPARα and dual PPARα/γ activation recruited UCP1+ beige adipocytes and favored UCP1-independent thermogenesis, yielding body mass and insulin sensitivity normalization. Preserved mitochondrial metabolism emerges as a potential target for obesity treatment using PPAR agonists, with possible clinical applications.

Long-term hepatic damage in high-fructose-fed C57BL/6 mice: hepatic fibrogenesis, endoplasmic reticulum stress markers, and fibrosis.

The rising fructose intake in sugar-sweetened beverages and ultra-processed foods relates to the high incidence of nonalcoholic fatty liver disease. This study aimed to examine the effects of long-term high-fructose diet intake (for 16 or 20 weeks) on progressive hepatic damage, focusing on the endoplasmic reticulum stress markers and fibrogenesis as possible triggers of liver fibrosis. Forty 3-month-old male C57BL/6J mice were randomly divided into four nutritional groups: C16 (control diet for 16 weeks), C20 (control diet for 20 weeks), HFRU16 (high-fructose diet for 16 weeks), and HFRU20 (high-fructose diet for 20 weeks). Both HFRU groups showed oral glucose intolerance and insulin resistance, but only the HFRU20 group exhibited increased inflammation. The increased lipogenic and endoplasmic reticulum stress markers triggered hepatic fibrogenesis. Hence, time-dependent perivascular fibrosis with positive immunostaining for alpha-smooth muscle actin and reelin in HFRU mice was observed, ensuring fibrosis development in this mouse model. Our study showed time-dependent and progressive damage on hepatic cytoarchitecture, with maximization of hepatic steatosis without overweight in HFRU20 mice. ER stress and liver inflammation could mediate hepatic stellate cell activation and fibrogenesis, emerging as targets to prevent NAFLD progression and fibrosis onset in this dietary model.

Effectiveness of Cerium Oxide Nanoparticles in Non-Alcoholic Fatty Liver Disease Evolution Using In Vivo and In Vitro Studies: A Systematic Review.

Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of liver abnormalities, from benign steatosis to nonalcoholic steatohepatitis (NASH). Because of their antioxidant capabilities, CeNPs have sparked a lot of interest in biological applications. This review evaluated the effectiveness of CeNPs in NAFLD evolution through in vivo and in vitro studies. Databases such as MEDLINE, EMBASE, Scopus, and Web of Science were looked for studies published between 2012 and June 2023. Quality was evaluated using PRISMA guidelines. We looked at a total of nine primary studies in English carried out using healthy participants or HepG2 or LX2 cells. Quantitative data such as blood chemical markers, lipid peroxidation, and oxidative status were obtained from the studies. Our findings indicate that NPs are a possible option to make medications safer and more effective. In fact, CeNPs have been demonstrated to decrease total saturated fatty acids and foam cell production (steatosis), reactive oxygen species production and TNF-α (necrosis), and vacuolization in hepatic tissue when used to treat NAFLD. Thus, CeNP treatment may be considered promising for liver illnesses. However, limitations such as the variation in durations between studies and the utilization of diverse models to elucidate the etiology of NAFLD must be considered. Future studies must include standardized NAFLD models.

Role of long-chain polyunsaturated fatty acids, eicosapentaenoic and docosahexaenoic, in the regulation of gene expression during the development of obesity: a systematic review.

Introduction: There exists a correlation between obesity and the consumption of an excessive amount of calories, with a particular association between the intake of saturated and trans fats and an elevated body mass index. Omega-3 fatty acids, specifically eicosapentaenoic and docosahexaenoic acids, have been identified as potential preventive nutrients against the cardiometabolic hazards that are commonly associated with obesity. The objective of this comprehensive review was to elucidate the involvement of long-chain polyunsaturated fatty acids, specifically eicosapentaenoic acid and docosahexaenoic acid, in the modulation of gene expression during the progression of obesity. Methods: The present analysis focused on primary studies that investigated the association between long-chain polyunsaturated fatty acids, gene expression, and obesity in individuals aged 18 to 65 years. Furthermore, a comprehensive search was conducted on many databases until August 2023 to identify English-language scholarly articles utilizing MeSH terms and textual content pertaining to long-chain polyunsaturated fatty acids, gene expression, obesity, and omega-3. The protocol has been registered on PROSPERO under the registration number CRD42022298395. A comprehensive analysis was conducted on a total of nine primary research articles. All research collected and presented quantitative data. Results and Discussion: The findings of our study indicate that the incorporation of eicosapentaenoic and docosahexaenoic acid may have potential advantages and efficacy in addressing noncommunicable diseases, including obesity. This can be attributed to their anti-inflammatory properties and their ability to regulate genes associated with obesity, such as PPARγ and those within the ALOX family. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022298395, CRD42022298395.

Peroxisome proliferator-activated receptors as targets to treat metabolic diseases: Focus on the adipose tissue, liver, and pancreas.

The world is experiencing reflections of the intersection of two pandemics: Obesity and coronavirus disease 2019. The prevalence of obesity has tripled since 1975 worldwide, representing substantial public health costs due to its comorbidities. The adipose tissue is the initial site of obesity impairments. During excessive energy intake, it undergoes hyperplasia and hypertrophy until overt inflammation and insulin resistance turn adipocytes into dysfunctional cells that send lipotoxic signals to other organs. The pancreas is one of the organs most affected by obesity. Once lipotoxicity becomes chronic, there is an increase in insulin secretion by pancreatic beta cells, a surrogate for type 2 diabetes mellitus (T2DM). These alterations threaten the survival of the pancreatic islets, which tend to become dysfunctional, reaching exhaustion in the long term. As for the liver, lipotoxicity favors lipogenesis and impairs beta-oxidation, resulting in hepatic steatosis. This silent disease affects around 30% of the worldwide population and can evolve into end-stage liver disease. Although therapy for hepatic steatosis remains to be defined, peroxisome proliferator-activated receptors (PPARs) activation copes with T2DM management. Peroxisome PPARs are transcription factors found at the intersection of several metabolic pathways, leading to insulin resistance relief, improved thermogenesis, and expressive hepatic steatosis mitigation by increasing mitochondrial beta-oxidation. This review aimed to update the potential of PPAR agonists as targets to treat metabolic diseases, focusing on adipose tissue plasticity and hepatic and pancreatic remodeling.

Exercise prevents obesity by reducing gut-derived inflammatory signals to brown adipocytes in mice.

Gut dysbiosis impairs nonshivering thermogenesis (NST) in obesity. The antiobesogenic effects of exercise training might involve the modulation of gut microbiota and its inflammatory signals to the brown adipose tissue (BAT). This study evaluated whether high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) prevent overweight through reduced gut-derived inflammatory signals to BAT in high-fat-fed mice. Sixty male C57BL/6 mice (3 months old) comprised six experimental groups: control (C) diet group, C diet + HIIT (C-HIIT) group, C diet + MICT (C-MICT) group, high-fat (HF) diet group, HF diet + HIIT (HF-HIIT) group, and HF diet + MICT (HF-MICT) group. The protocols lasted for 10 weeks. HIIT and MICT restored body mass, mitigated glucose intolerance, and prevented hyperinsulinemia in HF-trained groups. A chronic HF diet caused dysbiosis, but HIIT and MICT prevented gut dysbiosis and preserved tight junction (TJ) gene expression. HF-HIIT and HF-MICT groups exhibited a similar pattern of goblet cell distribution, agreeing with the decreased plasma lipopolysaccharide concentrations and interscapular BAT (iBAT) Lbp-Cd14-Tlr4 expression. The lowered Nlrp3 and Il1ß in the HF-HITT and HF-MICT groups complied with iBAT thermogenic capacity maintenance. This study shows reliable evidence that HIIT and MICT prevented overweight by restoring the diversity of the gut microbiota phyla and TJ gene expression, thereby reducing inflammatory signals to brown adipocytes with preserved thermogenic capacity. Both exercise modalities prevented overweight, but HIIT rescued Zo-1 and Jam-a gene expression, exerting more potent anti-inflammatory effects than MICT (reduced LPS concentrations), providing a sustained increase in thermogenesis with 78% less distance traveled.

Coffee consumption prevents obesity-related comorbidities and attenuates brown adipose tissue whitening in high-fat diet-fed mice.

This study aimed to evaluate the preventive and therapeutic effects of coffee consumption on molecular changes and adipose tissue remodeling in a murine model of high-fat diet-induced obesity. Three-month-old C57BL/6 mice were initially divided into three groups, namely, control (C), high-fat (HF), and coffee prevention (HF-CP) groups, and the HF group was subdivided at the end of the 10th week into two subgroups, an HF group and a coffee treatment (HF-CT) group; thus, a total of four groups were investigated at the 14th week of the experiment. The HF-CP group had lower body mass than the HF group (-7%, P < .05) and a better distribution of adipose tissue. Both groups that received coffee (HF-CP and HF-CT) showed improved glucose metabolism compared with the HF group. Coffee consumption also attenuated adipose tissue inflammation and showed decreased macrophage infiltration and lower IL-6 levels compared with the HF group (HF-CP: -337% %, P < .05; HF-CT: -275%, P < .05). Hepatic steatosis and inflammation were attenuated in the HF-CP and HF-CT groups. The HF-CP group showed more pronounced expression of genes involved in adaptive thermogenesis and mitochondrial biogenesis (PPARγ, Prdm16, Pcg1α, ß3-adrenergic receptor, Ucp-1, and Opa-1) than the other experimental groups. Preventive coffee consumption associated with a high-fat diet ameliorates the metabolic profile related to the development of obesity and its comorbidities.

Chronic Excessive Fructose Intake Maximizes Brown Adipocyte Whitening but Causes Similar White Adipocyte Hypertrophy Than a High-Fat Diet in C57BL/6 Mice.

Objective: This study aimed to evaluate the differential role of a high-fat diet (HF) or high-fructose diet (HFRU) on white adipose tissue and brown adipose tissue remodeling in C57BL/6 mice.Methods: The animals were randomly assigned to receive HF (50% of energy as lipids), HFRU (50% of energy as fructose), or a control diet (C, 10% of energy as lipids) for 12 weeks. Results: The HF group became overweight from the 7th week onwards, but both HF and HFRU groups showed hyperinsulinemia, oral glucose intolerance, and adverse adipose tissue remodeling. HF and HFRU groups showed interscapular brown adipose tissue whitening, tough the reduced QA [nuclei] suggested maximized brown adipocyte dysfunction due to the HFRU diet. In contrast, HF and HFRU diets exerted similar effects upon subcutaneous white adipocytes, with a similar average cross-sectional area. Immunohistochemistry confirmed the whitening enhancement with reduced UCP1 immunodensity in the HFRU group. Conclusion: In conclusion, HF and HFRU diets had indistinguishable effects upon white adipocyte morphology, but the HFRU diet provoked a more pronounced whitening than the HF diet after a 12-week protocol. These results point to the silent and harmful impact that excessive fructose has upon the metabolism of lean mice.

Effectiveness of mRNA, protein subunit vaccine and viral vectors vaccines against SARS-CoV-2 in people over 18 years old: a systematic review.

INTRODUCTION: Vaccines prevent disease and disability; save lives and represent a good assessment of health interventions. Several systematic reviews on the efficacy and effectiveness of COVID-19 vaccines have been published, but the immunogenicity and safety of these vaccines should also be addressed. AREAS COVERED: This systemic investigation sought to explain the efficacy, immunogenicity, and safety of new vaccination technologies against SARS-CoV-2 in people over 18 years old. Original research studying the effectiveness on mRNA, protein subunit vaccines, and viral vector vaccines against SARS-CoV-2 in people over 18 years old was analyzed. Several databases (Web of Science, Scopus, MEDLINE and EMBASE) were searched between 2012 and November 2022 for English-language papers using text and MeSH terms related to SARS-CoV-2, mechanism, protein subunit vaccine, viral vector, and mRNA. The protocol was registered on PROSPERO, CRD42022341952. Study quality was assessed using the NICE methodology. We looked at a total of six original articles. All studies gathered and presented quantitative data. EXPERT OPINION: Our results suggest that new vaccinations could have more than 90% efficacy against SARS-CoV-2, regardless of the technology used. Furthermore, adverse reactions go from mild to moderate, and good immunogenicity can be observed for all vaccine types.

Peroxisome proliferator-activated receptors-alpha and gamma synergism modulate the gut-adipose tissue axis and mitigate obesity.

AIM: To evaluate the effects of single PPARα or PPARγ activation, and their synergism (combined PPARα/γ activation) upon the gut-adipose tissue axis, focusing on the endotoxemia and upstream interscapular brown adipose tissue (iBAT) function in high-saturated fat-fed mice. METHODS: Male C57BL/6 mice received a control diet (C, 10% lipids) or a high-fat diet (HF, 50% lipids) for 12 weeks. Then, the HF group was divided to receive the treatments for four weeks: HFγ (pioglitazone, 10 mg/kg), HFα (WY-14643, 3.5 mg/kg), and HFα/γ (tesaglitazar, 4 mg/kg). RESULTS: The HF group exhibited overweight, oral glucose intolerance, gut dysbiosis, altered gut permeability, and endotoxemia, culminating in iBAT whitening. The downregulation of LPS-Tlr4 signaling underpinned reduced inflammation and improved lipid metabolism in iBAT in the HFα/γ group, the unique to show normalized body mass and increased energy expenditure. CONCLUSION: PPARα/γ synergism treated obesity by ameliorating the gut-adipose tissue axis, where restored gut microbiota and permeability controlled endotoxemia and rescued iBAT whitening through favored thermogenesis.

Brown adipose tissue as an endocrine organ: updates on the emerging role of batokines.

Brown adipose tissue (BAT) remains active in adults, oxidizing fatty acids or glucose and releasing energy in the form of heat. Brown adipocytes and enhanced thermogenesis are targets for treating obesity and its comorbidities. BAT shows high synthesis activity and secretes several signaling molecules. The brown adipokines, or batokines, take action in an autocrine, paracrine, and endocrine manner. Batokines have a role in the homeostasis of the cardiovascular system, central nervous system, white adipose tissue, liver, and skeletal muscle and exert beneficial effects on BAT. The systemic function of batokines gives BAT an endocrine organ profile. Besides, the batokines Fibroblast Growth Factor-21, Vascular Endothelial Growth Factor A, Bone Morphogenetic Protein 8, Neuregulin 4, Myostatin, and Interleukin-6 emerge as targets to treat obesity and its comorbidities, deserving attention. This review outlines the role of six emerging batokines on BAT and their cross-talk with other organs, focusing on their physiological significance and diet-induced changes.

Semaglutide (GLP-1 receptor agonist) stimulates browning on subcutaneous fat adipocytes and mitigates inflammation and endoplasmic reticulum stress in visceral fat adipocytes of obese mice.

Semaglutide (GLP-1 agonist) was approved for treating obesity. Although the effects on weight loss and metabolism are known, the responses of adipocytes to semaglutide are yet limited. C57BL/6 male mice (n = 20/group) were fed a control diet (C) or a high-fat (HF) diet for 16 weeks and then separated into four groups (n = 10/group) for an additional four weeks: C, C diet and semaglutide, HF, and HF diet and semaglutide. Epididymal white adipose tissue (eWAT) and subcutaneous white adipose tissue (sWAT) fat pads were studied with biochemistry, immunohistochemistry/fluorescence, stereology, and reverse transcription-quantitative polymerase chain reaction. In obese mice, semaglutide reduced the fat pad masses (eWAT, -55%; sWAT, -40%), plasmatic cytokines, and proinflammatory gene expressions: tumor necrosis factor-alpha (-60%); interleukin (IL)-6 (-55%); IL-1 beta (-40%); monocyte chemoattractant protein-1 (-90%); and leptin (-80%). Semaglutide also lessened endoplasmic reticulum (ER) stress genes of activating transcription factor-4 (-85%), CCAAT enhancer-binding protein homologous protein (-55%), and growth arrest and DNA damage-inducible gene 45 (-45%). The obese mice's adipocyte hypertrophy and macrophage infiltration were equally reduced by semaglutide. Semaglutide enhanced multiloculation and uncoupled protein 1 (UCP1) labeling in obese mice: peroxisome proliferator-activated receptor-alpha (+560%) and gamma (+150%), fibronectin type III domain-containing protein 5 (+215%), peroxisome proliferator-activated receptor-alpha coactivator (+110%), nuclear respiratory factor 1 (+260%), and mitochondrial transcription factor A (+120%). Semaglutide also increased thermogenetic gene expressions for the browning phenotype maintenance: beta-3 adrenergic receptor (+520%), PR domain containing 16 (+90%), and Ucp1 (+110%). In conclusion, semaglutide showed significant beneficial effects beyond weight loss, directly on fat pads and adipocytes of obese mice, remarkably anti-inflammatory, and reduced adipocyte size and ER stress. Besides, semaglutide activated adipocyte browning, improving UCP1, mitochondrial biogenesis, and thermogenic marker expressions help weight loss.

Effectiveness of Copper Nanoparticles in Wound Healing Process Using In Vivo and In Vitro Studies: A Systematic Review.

Chronic wounds are defined as wounds that do not heal in an orderly and timely manner through the various stages of the healing process. Copper nanoparticles are essential in dressings for wound healing because they promote angiogenesis and skin regeneration, which hasten the healing process. This systematic investigation sought to explain how copper nanoparticles affect chronic wound healing in vivo and in vitro. We realized a systematic review of original articles studying the effectiveness of copper nanoparticles in the healing process of chronic wounds. The protocol was registered in the PROSPERO database. Several databases were searched between 2012 and January 2022 for English-language papers using MeSH terms and text related to chronic wounds, copper nanoparticles, and wound healing. Quality was evaluated using National Institute for Health and Care Excellence methodology and PRISMA guidelines. We looked at a total of 12 primary studies. Quantitative data were gathered and presented in all studies. Our results suggest that copper nanoparticles could have an excellent healing property, facilitating the liberation of growth factors that help the anti-inflammatory process of the wound and significantly improving antibacterial and antioxidant activities. In addition, copper presents a higher biocompatibility than other metallic ions, promoting regeneration and increasing skin quality.