White Adipose Tissue Weight Research Articles

Additive impact of soy protein dietary intake and exercise on visceral fat mass reduction and mitochondrial complex I activation in skeletal muscle.

Soy protein has shown remarkable effectiveness in reducing fat mass compared with other protein sources, and exercise has the potential to further enhance this fat loss effect. Previous studies have demonstrated that soy protein intake leads to decreased fatty acid synthesis, which contributes to its fat-loss properties. However, the exact mechanism by which these lipids are consumed remains unclear. To investigate this, we conducted a comprehensive study using C57/BL6 male mice, comparing the effects of soy and casein proteins with and without exercise (Casein-Sed, Casein-Ex, Soy-Sed, and Soy-Ex groups) under high- and low-protein conditions (14% or 40% protein). Our findings revealed that combining soy protein intake with exercise significantly reduced epididymal white adipose tissue (eWAT) weight, particularly in the high-protein diet group. Further analysis revealed that exercise increased the expression of lipid oxidation-regulatory proteins, including mitochondrial oxidative phosphorylation protein (OXPHOS) complexes, in the plantaris muscle regardless of the protein source. Although soy protein intake did not directly affect muscle mitochondrial protein expression, the activity of OXPHOS complex I was additively enhanced by exercise and soy protein under the 40% protein condition. Notably, complex I activity inversely correlated with eWAT weight in the soy protein diet group. These results highlight the potential link between improved complex I activity induced by soy protein and fat mass reduction, which emphasizes the promising benefits of combining soy protein with exercise in promoting fat loss.NEW & NOTEWORTHY The findings revealed that soy protein intake combined with exercise resulted in reduced adipose tissue weight compared with that obtained with casein protein intake. Furthermore, the joint impact of exercise and soy protein consumption resulted in enhanced activity of oxidative phosphorylation protein (OXPHOS) complex I in fast-twitch muscles, which appears to be associated with fat mass reduction. These findings elucidate the potential additive effects of soy protein and exercise on body weight management.

Centella asiatica lowers body fat accumulation via regulating cholesterol homeostasis- and lipid metabolism-related genes in mice with high-fat, high-sugar diet-induced obesity

To understand the mechanisms involved in the anti-obesity effects Centella asiatica (CA), we examined body weight, serum levels, white adipose tissue (WAT) weight, histological analysis, and the expression of cholesterol homeostasis- and lipid metabolism-related genes in mice with high-fat, high-sugar diet (HFHSD)-induced obesity that were orally treated with CA for 12 weeks. Eight-week-old, male C57BL/6J mice were assigned to the following four groups (8 mice/group): NOR, normal diet; HFHSD (Control), HFHSD; CA-L, HFHSD + CA 300 mg/kg; CA-H, HFHSD+CA 600 mg/kg. The suspension of powdered CA leaf was fed using oral gavage. CA treatment significantly attenuated HFHSD-induced increase in body weight gain, serum glucose, triacylglycerol, and WAT weight (p < 0.05). Compared to that in HFHSD, adipocyte diameter and macrovesicular area of epididymal WAT significantly decreased with CA treatment (p < 0.05). The mRNA expression levels of peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), cluster of differentiation 36 (CD36), 3- hydroxyl-3-methylglutaryl CoA reductase (HMGCR), and stearoyl CoA desaturase 1 (SCD 1) were significantly downregulated in the CA-H compared to the HFHSD (p < 0.05). CA exerts anti-obesity effects by lowering body fat accumulation via regulating gene expression and thus, is a potential lipid-lowering agent.

Characterization of metabolic phenotypes and distinctive genes in mice with low-weight gain.

Being overweight exacerbates various metabolic diseases, necessitating the identification of target molecules for obesity control. In the current study, we investigated common physiological features related to metabolism in mice with low weight gain: (1) G protein-coupled receptor, family C, group 5, member B-knockout; (2) gastric inhibitory polypeptide receptor-knockout; and (3) Iroquois-related homeobox3-knockout. Moreover, we explored genes involved in metabolism by analyzing differentially expressed genes (DEGs) between low-weight gain mice and the respective wild-type control mice. The common characteristics of the low-weight gain mice were low inguinal white adipose tissue (iWAT) and liver weight despite similar food intake along with lower blood leptin levels and high energy expenditure. The DEGs of iWAT, epididymal (gonadal) WAT, brown adipose tissue, muscle, liver, hypothalamus, and hippocampus common to these low-weight gain mice were designated as candidate genes associated with metabolism. One such gene tetraspanin 7 (Tspan7) from the iWAT was validated using knockout and overexpressing mouse models. Mice with low Tspan7 expression gained more weight, while those with high Tspan7 expression gained less weight, confirming the involvement of the Tspan7 gene in weight regulation. Collectively, these findings suggest that the candidate gene list generated in this study contains potential target molecules for obesity regulation. Further validation and additional data from low-weight gain mice will aid in understanding the molecular mechanisms associated with obesity.

Abstract 14169: Deletion of P21 Activated Kinase-1 Modulates Energy Homeostasis and Affects Cardiac Function

Introduction: We investigated the consequences of P21-activated kinase-1 (PAK1) deletion on cardiac function, body weight, body composition, and energy balance using a mouse model of global PAK1 knock out. PAK1 is a protein kinase that plays a role in multiple aspects of cardiac health. We hypothesize that PAK1 plays a role in cardiometabolic health including cardiac function and adipose tissue homeostasis. Methods: We used PAK1 -/- in the FVB/N background. We included 10-12-week-old male and female mice. Age and sex-matched FVB/N mice were used as wild-type (WT) controls. Most results included both male and female mice together, as no differences were found between sexes. Ca 2+ kinetics was measured in neonatal cardiomyocytes. Results: Deletion of PAK1 was found to have a significant impact on cardiac function. Specifically, slower Ca 2+ release and reuptake kinetics accompanied with decreased phospholamban phosphorylation was observed in PAK1 -/- mice. These changes affected cardiac systolic (EF, s’) and lusitropy parameters (E/e’, IVRT). Moreover, our findings revealed body weight differences between PAK1 -/- and WT at 12 weeks, accompanied with increased % fat mass and decreased % lean mass in PAK1 -/- , indicating a shift towards adiposity. Further analysis revealed that PAK1 -/- mice had increased weights of white adipose tissue (WAT), and brown adipose tissue (BAT). Moreover, we found increased food intake, increased number of feeding bouts and decreased energy expenditure accompanied with decreased thermogenic markers in subcutaneous WAT and BAT in PAK1 -/- , further contributing to the obesogenic phenotype (see table for results). Conclusions: Deletion of PAK1 affected systolic and diastolic functions, and resulted in increased energy intake, decreased energy expenditure, and increased adiposity. Therefore, targeting PAK1 signaling pathways may represent a promising therapeutic strategy for improving cardiometabolic diseases.

Pioglitazone-Enhanced Brown Fat Whitening Contributes to Weight Gain in Diet-Induced Obese Mice.

Pioglitazone is an insulin sensitizer used for the treatment of type 2 diabetes mellitus (T2DM) by activating peroxisome proliferator-activated receptor gamma. This study aimed to investigate the effects of pioglitazone on white adipose tissue (WAT) and brown adipose tissue (BAT) in diet-induced obese (DIO) mice. C57BL/6 mice were treated with pioglitazone (30 mg/kg/day) for 4 weeks after a 16-week high-fat diet (HFD) challenge. Body weight gain, body fat mass, energy intake, and glucose homeostasis were measured during or after the treatment. Histopathology was observed by hematoxylin and eosin, oil red O, immunohistochemistry, and immunofluorescence staining. Expression of thermogenic and mitochondrial biogenesis-related genes was detected by quantitative real-time PCR and western blotting. After 4-week pioglitazone treatment, the fasting blood glucose levels, glucose tolerance, and insulin sensitivity were significantly improved, but the body weight gain and fat mass were increased in DIO mice. Compared with the HFD group, pioglitazone did not significantly affect the weights of liver and WAT in both subcutaneous and epididymal regions. Unexpectedly, the weight of BAT was increased after pioglitazone treatment. Histological staining revealed that pioglitazone ameliorated hepatic steatosis, reduced the adipocyte size in WAT, but increased the adipocyte size in BAT. Though pioglitazone can promote lipolysis, thermogenesis, and mitochondrial function in WAT, it leads to impaired thermogenesis, and mitochondrial dysfunction in BAT. In conclusion, pioglitazone could promote the browning of WAT but led to the whitening of BAT; the latter might be a new potential mechanism of pioglitazone-induced weight gain during T2DM treatment.

Dietary Phospholipids Alleviate Diet-Induced Obesity in Mice: Which Fatty Acids and Which Polar Head.

The weight loss effects of dietary phospholipids have been extensively studied. However, little attention has been paid to the influence of phospholipids (PLs) with different fatty acids and polar headgroups on the development of obesity. High-fat-diet-fed mice were administrated with different kinds of PLs (2%, w/w) with specific fatty acids and headgroups, including EPA-enriched phosphatidylcholine/phosphatidylethanolamine/phosphatidylserine (EPA-PC/PE/PS), DHA-PC/PE/PS, Egg-PC/PE/PS, and Soy-PC/PE/PS for eight weeks. Body weight, white adipose tissue weight, and the levels of serum lipid and inflammatory markers were measured. The expression of genes related to lipid metabolism in the liver were determined. The results showed that PLs decreased body weight, fat storage, and circulating lipid levels, and EPA-PLs had the best efficiency. Serum TNF-α, MCP-1 levels were significantly reduced via treatment with DHA-PLs and PS groups. Mechanistic investigation revealed that PLs, especially EPA-PLs and PSs, reduced fat accumulation through enhancing the expression of genes involved in fatty acid β-oxidation (Cpt1a, Cpt2, Cd36, and Acaa1a) and downregulating lipogenesis gene (Srebp1c, Scd1, Fas, and Acc) expression. These data suggest that EPA-PS exhibits the best effects among other PLs in terms of ameliorating obesity, which might be attributed to the fatty acid composition of phospholipids, as well as their headgroup.

THU507 Tumor Activin A Mediates Cachexia Primarily Through White Adipose Tissue Hydrolysis In Pancreatic Ductal Adenocarcinoma

Abstract Disclosure: S. Yu: None. Y. Luan: None. R. Dong: None. A. Abazarikia: None. S. Kim: None. Pancreatic ductal adenocarcinoma (PDAC) commonly harbors mutations in KRAS and TP53 genes and its overall 5-year survival rate is only 10% in the US. Among risk factors associated with the dismal PDAC prognosis, cachexia accounts for about 30% of PDAC-related death and is present in nearly 80% of PDAC patients. Significant adipose tissue loss followed by skeletal muscle loss characterizes PDAC-related cachexia in humans and mice. Accumulated evidence indicates that activin A, a homodimer of inhibin βA that is encoded by the INHBA gene, is a recognized key cachexia mediator as supported by mitigation of weight loss by activin A antagonists in PDAC-bearing mice. However, much remains unclear regarding the primary source cells of activin A and the mechanisms by which activin A mediates cachexia in PDAC. To address the unknowns, we employed CRISPR/Cas9 system for Inhba gene knock-down (KD) in mouse KPC (KrasG12D and Trp53R172H) PDAC cells and generated orthotopic mice using Inhba KD or control KPC cells. Sham group which received the same operation except for cell injection was included. Body weight was measured on a daily basis, and blood and white adipose tissues (WATs) and skeletal muscle tissues were harvested on post-surgery day 12. We found that, when compared to the Sham group, injection of control KPC cells significantly elevated serum activin A levels up to 6 ng/mL and temporally decreased the average body weight in the orthotopic mice (Ctrl group), whereas Inhba gene KD significantly reduced serum activin A levels by ∼ 2 ng/mL and prevented weight loss in the orthotopic mice (KD group). When compared to the Sham and KD groups, notable reductions in organ weights of epididymal, mesenteric or subcutaneous WATs were found in the Ctrl group, however, weights for gastrocnemius and plantaris or soleus muscle tissues were statistically similar between the Ctrl and KD groups at post-surgery day 12. Correspondingly, the average serum free fatty acids levels were higher in the Ctrl group than the KD group. Histological observations support that dramatic adipocyte size reductions in WATs were prevented by serum activin A suppression. Immunofluorescence analysis showed that WATs from the Ctrl group had considerably higher protein expression of hormone-sensitive or adipose triglyceride lipase than the KD and Sham groups. Furthermore, phosphorylation of SMAD3 and phosphorylated PKA substrate which regulate adipocyte lipolysis were intensely stained in WATs from the Ctrl group when compared to the KD and Sham groups. Collectively, our findings identify PDAC cancer cells as the major source of activin A in PDAC and suggest systemic activin A as a potential mediator of PDAC-related adipose tissue loss. The current findings warrant further investigation to address clinical relevance. Presentation: Thursday, June 15, 2023

SAT649 Org43553, The First Low-molecular-weight Agonist Of The Human Luteinizing Hormone Receptor Induces Leanness And Energy Expenditure In Mice

Abstract Disclosure: D. Lizneva: None. A. Gumerova: None. K. Ievleva: None. O. Barak: None. F. Korkmaz: None. J. Gimenez Roig: None. T. Frolinger: None. G. Pevnev: None. F. Sultana: None. N. Kramskiy: None. S. Wizman: None. M. Orloff: None. A.R. Pallapati: None. S. Rojekar: None. V. Ryu: None. O. Moldavski: None. T. Yuen: None. M. Zaidi: None. We provide compelling evidence that LH is a pro–lean hormone, and that ORG43553, the first low-molecular-weight agonist of the luteinizing hormone receptor (LHCGR) induces leanness and promotes energy expenditure in mice. We detected Lhcgr transcripts in white adipose tissue (WAT) depots in male and female C57BL/6 mice (qPCR, IHC, RNAscope, Sanger sequencing), but not in Lhcgr-/- mice. Intraperitoneal AlexaFluor-488–labeled hCG bound to gonadal and subcutaneous fat pads in wild type mice, but not in Lhcgr-/- mice. Following i.v. 89Zr–LH injection, radioactivity was detected in mesenteric, inguinal and gonadal WAT. LH, hCG and ORG43553 rapidly induced ERK1/2 phosphorylation in differentiated 3T3.L1 cells. Female and male Lhcgr+/- mice on normal chow and high–fat diet, respectively, became obese, importantly, without changes in sex steroids. The gene–dosage effect of Lhcgr depletion suggests a dominant physiologic action of LH on body composition. 14–week–old male C57BL/6 mice were fed on high–fat diet and injected, i.p., with LH, hCG or vehicle, twice–a–week, for 6 weeks. Both LH and hCG markedly reduced body fat accrual (qNMR) but triggered a rise in serum testosterone. The hCG–induced lean phenotype persisted despite androgen receptor blockade by flutamide—confirming that the pro–lean actions of LH and hCG were largely independent of testosterone. Furthermore that LH failed to inhibit fat accrual in Lhcgr-/- mice testified to its action via the LHCGR. Injection of ORG43553 into male C57BL/6 mice for 9 weeks caused a significant reduction in fat mass (qNMR), with reduced WAT weight in fat depots. Remarkably, serum testosterone remained unchanged confirming that the anti–adiposity effect of ORG43553 was independent of testosterone. To study the mechanism of LHCGR activation on body fat, 3T3.L1 adipocytes were treated with hCG or ORG43553 for 12 hours. This resulted in reduced oil droplet accumulation. 3T3-L1–derived organoids treated with LH, hCG or ORG43553 also displayed a substantial reduction in the differentiated layer compared to vehicle–treated organoids. To study whether, in addition to reducing adipocyte differentiation, LHCGR agonism also enhanced thermogenesis, 3T3-L1 adipocytes were pretreated with ORG43553 for 1 hour before measuring oxygen consumption rate (OCR) on a Seahorse Xf96 Analyzer. ORG43553 increased OCR at baseline and upon oligomycin exposure, indicating mitochondria proton leak (thermogenesis). To confirm increased energy expenditure in vivo, mice were injected, s.c., with ORG43553 or vehicle. Oxygen consumption (VO2) and energy expenditure (EE) increased acutely in ORG43553–treated mice, with no change in locomotor activity. The findings suggest that ORG45335, which has been tested in humans for infertility, can potentially become a candidate drug for obesity. Presentation: Saturday, June 17, 2023

Dietary Bamboo Charcoal Decreased Visceral Adipose Tissue Weight by Enhancing Fecal Lipid Excretions in Mice with High-Fat Diet-Induced Obesity.

Bamboo charcoal (BC) powder is prepared from thick bamboo stems via dry distillation and is often used for food coloring. Due to the unique structure of the micropores in bamboo stems, BC powder also serves as an indigestible carrier to prevent the absorption of toxic substances and nutrients from the digestive tract. This study evaluated the health-promoting function of BC, particularly its effects in decreasing visceral adipose tissue in a mouse model with high-fat diet (HFD)-induced obesity. Four-week-old male C57BL/6J mice were divided into three groups and fed either a low-fat (LF) diet (7% fat), HF diet (25% fat), or HF diet with 0.5% BC (HF-BC). After 80 days, the HF-BC diet was found to have decreased epididymal and mesenteric white adipose tissue weights compared to HFD. The inhibition of visceral fat accumulation by BC intake was partly due to enhanced fecal fatty acid excretion induced by its bile acid-binding and pancreatic lipase inhibition. Contrarily, the gut microbiota, known to influence systemic energy metabolism, did not change significantly between the HF and HF-BC groups. These results indicate that dietary BC inhibits visceral fat accumulation, which could reduce obesity development.

Association of Aquaporin 7 and 9 with Obesity and Fatty Liver in db/db Mice.

Aquaporin (AQP) 7 and AQP9 are membrane channel proteins called aquaglyceroporins and are related to glucose and lipid metabolism. AQP7 is mainly expressed in white adipose tissue (WAT) and is involved in releasing glycerol into the bloodstream. AQP9 is the glycerol channel in the liver that supplies glycerol to the hepatic cells. In this study, we investigated the relationship between the expression of aquaglyceroporins and lifestyle-related diseases, such as obesity and fatty liver, using 22-week-old db/db mice. Body weight, WAT, and liver weight showed increases in db/db mice. The levels of liver lipids, plasma lipids, insulin, and leptin were also increased in db/db mice. Gene expression related to fatty acid and triglyceride synthesis in the liver was enhanced in db/db mice. In addition, gene and protein expression of gluconeogenesis-related enzymes was increased. Conversely, lipolysis-related gene expression in WAT was reduced. In the db/db mice, AQP9 expression in the liver was raised; however, AQP7 expression in WAT was reduced. These results suggest that in db/db mice, enhanced hepatic AQP9 expression increased the supply of glycerol to the liver and induced fatty liver and hyperglycemia. Additionally, reduced AQP7 expression in WAT is associated with excessive lipid accumulation in adipocytes. Aquaglyceroporins are essential molecules for glucose and lipid metabolism, and may be potential target molecules for the treatment of obesity and lifestyle-related diseases.

Abstract P340: Codonopsis Lanceolata Extract Prevents Metabolic And Cardiovascular Alterations In Short-term High-fat/high-fructose Diet-fed Adolescent Rats

Fast food consumption, which has increased among adolescents, has been associated with the risk of cardio-metabolic disorders. However, the effects of short-term high-fat/high-fructose diet (HFFD) on cardiovascular and metabolic parameters in adolescent rats has not yet been evaluated. Also, preventive effects of codonopsis lanceolata (CL) in these rats are unknown. Therefore, we investigated the effects of short-term HFFD consumption on cardiovascular and metabolic factors in adolescent rats, as well as the preventive effects of CL extract. Adolescent rats were fed a 60% high-fat diet plus 10% fructose water for 2 weeks. During this time, CL extract (200 or 400 mg/kg) was administered once daily. Short-term HFFD increased visceral white adipose tissue (WAT) weight, fasting blood sugar (FBS) concentration and water intake in adolescent rats. This diet also significantly increased systolic blood pressure (SBP), heart rate, and phenylephrine-induced vasocontraction. CL extract, however, effectively reduced visceral WAT weight, FBS, SBP and heart rate in short-term HFFD-fed adolescent rats. These findings indicate that exposure to HFFD for only 2 weeks induced cardiovascular and metabolic alterations in adolescent rats and that CL extract is effective in preventing these harmful effects of short-term HFFD in adolescent rats. This work was by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2021R1A2C2004118). * Corresponding author. Keywords: high-fat/high-fructose diet; adolescent; codonopsis lanceolata ; prevention; visceral white adipose tissue; fasting blood sugar; systolic blood pressure

Cellular Evidence for Telocytes Mediating Electroacupuncture to Ameliorate Obesity in Mice.

Electroacupuncture has been generally applied to target obesity, the principle of which is based on the meridian in traditional Chinese medicine. Although Telocytes (TCs) have been reported as the potential essence of meridians, their specific role in the electroacupuncture treatment of obesity remains unclear. Thus, we investigated the cellular evidence for TC-mediated electroacupuncture to alleviate obesity. Mice were divided into three groups as follows: electroacupuncture group (EA), control group (CG), and normal group (NG). The present study showed that the weight of perirenal white adipose tissue (rWAT), the serum level of total cholesterol, and the low-density lipoprotein cholesterol were all significantly decreased after electroacupuncture. Ultrastructurally, the prolongations (telopodes, Tps) of TCs were in direct contact with adipocytes, and lipid droplets were distributed on the surface of Tps. The proportions of double-positive fluorescent areas of TCs (CD34 and PDGFRα) were significantly elevated with concomitant elongated Tps in EA mice, as compared to those in CG mice. The expression of Cx43 and CD63 (gap junction and exosome markers) was significantly enhanced. These characteristics facilitated the transmission of electroacupuncture stimulation from skin to rWAT. We conclude that electroacupuncture relieved obesity by activating TCs morphologically, upregulating the gap junctions between TCs, and increasing the exosomes around TCs.

Mouse Model of Anti-Obesity Effects of Blautia hansenii on Diet-Induced Obesity.

Reportedly, a relationship exists between intestinal microflora and obesity-related lifestyle diseases. Blautia spp. a major intestinal microbiota, accounts for 3-11% of human intestinal microflora. Epidemiological reports have described that people with more visceral fat have less Blautia hansenii in their intestinal tract irrespective of age or gender. However, the effect of oral administration of heat-sterilized Blautia hansenii on obesity has not been clarified. Therefore, the aim of this study was to evaluate the effects of dietary Blautia hansenii administration on obesity in high-fat-diet-induced obesity in a mouse model. Heat-sterilized cells of Blautia hansenii were used. C57BL/6J mice (normal mice, n = 7) were fed with each experimental diet for nine weeks. Diets for experimentation were: normal-fat (NF) diets, high-fat (HF) diets, and high-fat + Blautia hansenii (HF + Blautia) diets. The HF + Blautia group was administered about 1 × 109 (CFU/mouse/day) of Blautia hansenii. During the periods of experimentation, body weight, food intake, water consumption, and fecal weight were recorded, and glucose tolerance tests were performed. Subsequently, the white adipose tissue (WAT) weight and serum components were measured. Short-chain fatty acid contents in the feces and cecum were analyzed. Furthermore, changes in the intestinal microflora were analyzed using meta-genomics analysis. Results showed that the total weight of WAT in the HF + Blautia group was significantly lower (13.2%) than that of the HF group. Moreover, the HF + Blautia group exhibited better glucose tolerance than the HF group. Productivity of short-chain fatty acids in the intestinal tract was at a significantly (p < 0.05) low level in the HF group; on the other hand, it recovered in the HF + Blautia group. Furthermore, there was a higher ratio of Blautia (p < 0.05) in the intestinal tracts of the HF + Blautia group than in the HF group. These results suggest that Blautia hansenii administration suppresses obesity induced by a high-fat diet.

Malonate induces the browning of white adipose tissue in high-fat diet induced obesity model

Obesity increases the risk of various diseases, and many studies have examined prevention and treatment strategies. Browning of white adipocytes promotes triglyceride (TG) metabolism and is the new focus for treating obesity. This study investigated the role of malonate—a modulator of mitochondrial function—in adipocyte browning, and its potential as a therapeutic agent in obesity. Our findings revealed that malonate increased oxygen consumption without inhibiting ATP synthesis. Malonate induced expression of PRDM16—an important transcription factor for browning—and uncoupling protein 1 (beige adipocyte marker), suggesting that malonate induces browning in white adipocytes. In an obesity mouse model induced by a high-fat diet, malonate significantly reduced body weight and white adipose tissue weight, as well as improved insulin resistance. Importantly, malonate stimulated browning in white adipose tissue and maintained the mass of brown adipose tissue in the high-fat diet-induced obesity mouse model. We propose that manipulation of mitochondrial function by malonate is a promising therapeutic approach for obesity.

Lipopolysaccharide-induced persistent inflammation ameliorates fat accumulation by promoting adipose browning in vitro and in vivo

This work aimed to explore whether the persistent inflammation induced by lipopolysaccharide (LPS) ameliorates fat accumulation by promoting adipose browning in vitro and in vivo. LPS over 1 ng/mL reduced lipid accumulation while increasing the expressions of specific genes involved in inflammation, mitochondrial biogenesis, and adipose browning in 3T3-L1 adipocytes. Moreover, LPS in intraperitoneal injection decreased white adipose tissue weight and elevated interscapular brown adipose tissue weight in mice. According to RT-PCR and western blot analysis results, the expressions of genes and proteins related to inflammation, mitochondrial biogenesis, lipolysis, and brown or beige markers in different tissues were elevated after LPS intervention. Cumulatively, LPS-induced persistent inflammation may potentially ameliorate fat accumulation by facilitating adipose browning in 3T3-L1 adipocytes and mice. These results offer new perspectives into the effect of persistent inflammation induced by LPS on regulating fat metabolism, thereby reducing fat accumulation by boosting adipose browning procedure.

Sphingosine Kinase 2 Knockout Mice Resist HFD-Induced Obesity Through Increasing Energy Expenditure.

It has been reported that sphingosine kinase (SK) 2 plays a role in maintaining metabolism and glucose homeostasis. However, the mechanism remains uncertain. The present research aimed to further investigate the effect of SK2 knockout on high-fat diet (HFD)-induced obesity and metabolic regulation. Male SK2-/- and wild-type (WT) control mice were challenged with HFD for 8 weeks. Then, body composition, inguinal white adipose tissue (IWAT) histology, intraperitoneal glucose tolerance tests (IPGTT), and metabolic parameters were examined, and expression levels of uncoupling protein 1 (UCP1), a key molecular marker of thermogenesis, in IWAT were determined. After 8 weeks of HFD challenge, compared with WT mice, SK2-/- mice displayed decreased whole body, epididymal white adipose tissue (EWAT) and IWAT weights, reduced fat/lean body mass ratios and inguinal adipocytes size; also, SK2-/- mice exhibited improved intraperitoneal glucose tolerance. Next, elevated energy expenditure was observed in SK2-/- mice compared with WT mice; however, neither food intake nor physical activity showed obvious difference between SK2-/- and WT mice. Furthermore, we found that the expressions of UCP1 was markedly increased in IWAT from SK2-/- mice. SK2-/- mice may resist HFD-induced obesity through increasing energy expenditure by promoting thermogenesis in the beige adipose tissue.

The Effect of Fermented Momordica charantia with Leuconostoc mesenteroides MKSR on Metabolic Complications Induced by High-Fat High-Cholesterol Diet in C57BL/6 Mice

This study aimed to investigate the beneficial effects of Momordica charantia (MC) extract and MC fermented with Leuconostoc mesenteroides MKSR (FMC) on high-fat and high-cholesterol diet-induced metabolic complications. Male C57BL/6 mice were divided into six groups: normal diet (ND), high-fat and high-cholesterol diet (HFCD), HFCD with 1% MC extract (HFCD + 1M), HFCD with 4% MC extract (HFCD + 4M), HFCD with 1% fermented MC (HFCD + 1F), and HFCD with 4% fermented MC (HFCD + 4F). After 12 weeks of dietary intervention, the consumption of MC fermented with L. mesenteroides MKSR resulted in significant decreases in white adipose tissue weights (epididymal adipose tissue and retroperitoneal adipose tissue), serum alanine aminotransferase activity, and hepatic triglyceride levels. FMC also lowered total hepatic cholesterol content, improved glucose clearance during the oral glucose tolerance and insulin tolerance tests, and increased fecal cholesterol efflux from the enterohepatic circulation. Furthermore, the FMC notably increased hepatic mRNA expressions, which may indicate a compensatory mechanism against induced cholesterol efflux. Moreover, FMC induced both adipogenic (sterol regulatory element-binding protein 1c) and lipolytic (lipoprotein lipase, peroxisome proliferator-activated receptor alpha, and adiponectin) mRNA expressions. These findings suggest that fermentation with the probiotic L. mesenteroides MKSR enhances the beneficial effects of MC, preventing metabolic complications associated with a high-fat diet.

Increased cholesterol uptake is associated with the altered gene expression in white adipose tissue of ApoE−/− mice fed a high-fat high-cholesterol diet

Apolipoprotein E knock out (ApoE−/−) mice, the widely used model for atherosclerosis, exhibits anti-obesity characteristics due to the impaired lipoprotein internalization. Since excessive accumulation of triglycerides and cholesterol in white adipose tissue (WAT) is shown to increase the risk of metabolic diseases, we investigated the effects of dietary high-fat high-cholesterol (HFHC) on gene expression profile and the possible role of cholesterol accumulation in WAT of ApoE−/− mice. Control (CON) and HFHC diets were provided to wild-type mice (WC, WH) and ApoE−/− mice (EC, EH) for 10 weeks. Although body and WAT weights were lower in the ApoE−/− group compared to the wild-type group, increases in cholesterol and lipid peroxides in WAT were only observed in the ApoE−/− group. Transcriptome analysis revealed 3660 and 839 differentially expressed genes (DEGs) in the EC/WC and EH/WH comparison, respectively. “Thermogenesis” and “Oxidative phosphorylation” KEGG pathways were found in the EC/WC comparison, but not in the EH/WH comparison. We identified 142 and 2585 DEGs in the WH/WC and EH/EC comparison respectively, indicating a stronger effect of HFHC on WAT of ApoE−/− mice. Gene ontology analysis of DEGs revealed the association of DEGs with “Regulation of inflammatory response” term, in the EH/EC comparison, but not in the WH/WC comparison. Especially, genes encoding scavenger receptors and toll-like receptors were associated with cholesterol and lipid peroxide levels in WAT of ApoE−/− mice, but not in wild-type mice. In conclusion, changes in gene expression profile of WAT were more pronounced in ApoE−/− mice compared to wild-type mice in response to HFHC, and these altered genes were related to inflammatory response. These data suggest that increased cholesterol accumulation in WAT by dietary HFHC may play a pivotal role in the regulation of gene expression in ApoE−/− mice.

Mushroom Powder Ameliorates the Metabolic Syndromes by Maintaining Glucose and Lipid Homeostasis in High Sugar Diet-fed Mice

Diets high in added sugar both directly and indirectly promote the development of metabolic diseases such as diabetes and obesity. The objective of this study was to evaluate the effects of mushroom powder (MP) in preventing the development of metabolic disorders caused by a high sugar diet. Swiss albino male mice were fed with normal diet (ND) or high sugar diet (HSD) in supplementation with or without mushroom powder. The results showed that supplementation of MP in high sugar diet effectively reduced the food intake and body weight of mice. Moreover, MP sustained glucose tolerance in HSD-fed mice and a significantly lower glucose level was observed in the MP supplemented group than that of the HSD group. Furthermore, kidney and heart weight were almost similar among the groups. However, MP supplementation significantly reduced the liver weight in comparison to that of HSD control group. The wet weights of white adipose tissue and brown adipose tissue were also lower in the MP supplemented groups in comparison to that of HSD group. In addition, supplementation of MP in the high sugar diet significantly decreased the level of total cholesterol, triacylglycerides, and LDL content. In conclusion, these results suggest that mushroom powder was effective in preventing the development of diabetes and obesity induced by a high sugar diet. As mushroom powder is an abundant source of nutrients, therefore, this powder can be an important dietary supplement for treating metabolic disorders instigated by a high-sugar diet.&#x0D; J. of Sci. and Tech. Res. 4(1): 13-24, 2022

Green Tea Induces the Browning of Adipose Tissue—Systematic Review

Several foods and nutrients are being studied extensively because they have a positive effect on thermogenesis and the browning of white adipose tissue. Therefore, this study aims to evaluate, through a systematic review, the effect of green tea for inducing browning of adipose tissue. The systematic review was built following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyze. We searched the following electronic databases: PubMed (Medline), Science Direct, Scopus, and Web of Science. We included ten experimental articles that used green tea to treat induced obesity in rodents. Green tea reduced the weight of white and brown adipose tissue, positively regulated gene expression and microRNA that regulate the metabolism of adipose tissue, and morphological changes were identified as beige tissue. According to the results found, the factors involved in this induction to browning are PPARγ, PGC-1α, UCP1, CPT, and PRDM16. Therefore, green tea promotes the browning of adipose tissue in rodents. It is important to emphasize the need for studies in obese humans to identify whether the same metabolic response occurs.