Epididymal White Adipose Tissue Weight Research Articles

TRPV3 facilitates lipolysis and attenuates diet-induced obesity via activation of the NRF2/FSP1 signaling axis

Transient receptor potential vanilloid (TRPV) ion channels play a crucial role in various cellular functions by regulating intracellular Ca2+ levels and have been extensively studied in the context of several metabolic diseases. However, the regulatory effects of TRPV3 in obesity and lipolysis are not well understood. In this study, utilizing a TRPV3 gain-of-function mouse model (TRPV3G568V/G568V), we assessed the metabolic phenotype of both TRPV3G568V/G568V mice and their control littermates, which were randomly assigned to either a 12-week high-fat diet or a control diet. We investigated the potential mechanisms underlying the role of TRPV3 in restraining obesity and promoting lipolysis both in vivo and in vitro. Our findings indicate that a high-fat diet led to significant obesity, characterized by increased epididymal and inguinal white adipose tissue weight and higher fat mass. However, the gain-of-function mutation in TRPV3 appeared to counteract these adverse effects by enhancing lipolysis in visceral fat through the upregulation of the major lipolytic enzyme, adipocyte triglyceride lipase (ATGL). In vitro experiments using carvacrol, a TRPV3 agonist, demonstrated the promotion of lipolysis and antioxidation in 3T3-L1 adipocytes after TRPV3 activation. Notably, carvacrol failed to stimulate Ca2+ influx, lipolysis, and antioxidation in 3T3-L1 adipocytes treated with BAPTA-AM, a cell-permeable calcium chelator. Our results revealed that TRPV3 activation induced the action of transcriptional factor nuclear factor erythroid 2-related factor 2 (NRF2), resulting in increased expression of ferroptosis suppressor protein 1 (FSP1) and superoxide dismutase2 (SOD2). Moreover, the inhibition of NRF2 impeded carvacrol-induced lipolysis and antioxidation in 3T3-L1 adipocytes, with downregulation of ATGL, FSP1, and SOD2. In summary, our study suggests that TRPV3 promotes visceral fat lipolysis and inhibits diet-induced obesity through the activation of the NRF2/FSP1 signaling axis. We propose that TRPV3 may be a potential therapeutic target in the treatment of obesity.

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.

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.

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 Preventive Effect of Exercise and Oral Branched-Chain Amino Acid Supplementation on Obesity-Induced Brain Changes in Ldlr-/-.Leiden Mice.

Exercise and dietary interventions are promising approaches to tackle obesity and its obesogenic effects on the brain. We investigated the impact of exercise and possible synergistic effects of exercise and branched-chain amino acids (BCAA) supplementation on the brain and behavior in high-fat-diet (HFD)-induced obese Ldlr-/-.Leiden mice. Baseline measurements were performed in chow-fed Ldlr-/-.Leiden mice to assess metabolic risk factors, cognition, and brain structure using magnetic resonance imaging. Thereafter, a subgroup was sacrificed, serving as a healthy reference. The remaining mice were fed an HFD and divided into three groups: (i) no exercise, (ii) exercise, or (iii) exercise and dietary BCAA. Mice were followed for 6 months and aforementioned tests were repeated. We found that exercise alone changed cerebral blood flow, attenuated white matter loss, and reduced neuroinflammation compared to non-exercising HFD-fed mice. Contrarily, no favorable effects of exercise on the brain were found in combination with BCAA, and neuroinflammation was increased. However, cognition was slightly improved in exercising mice on BCAA. Moreover, BCAA and exercise increased the percentage of epididymal white adipose tissue and muscle weight, decreased body weight and fasting insulin levels, improved the circadian rhythm, and transiently improved grip strength. In conclusion, BCAA should be supplemented with caution, although beneficial effects on metabolism, behavior, and cognition were observed.

A transdermal treatment with MC903 ameliorates diet-induced obesity by reducing visceral fat and increasing myofiber thickness and energy consumption in mice

AimMC903 is a synthetic derivative of vitamin D3 that has been designed to diminish its impact on calcium metabolism and is clinically used as a transdermal reagent for psoriasis. Animal studies showed that an oral or intraperitoneal vitamin D3 treatment prevented the development of obesity. In contrast, the bioavailability of orally administered vitamin D3 is reported to be low in obese patients. In the current study, we aimed to investigate the impact of a transdermal treatment with MC903 in established obese mice. We further studied the underlying mechanisms of MC903-mediated metabolic improvement.Materials and methodsMale C57BL/6 J mice were fed standard chow or a 60% high-fat diet (HFD) for 7 weeks, and a transdermal treatment with MC903 on the ear auricle was initiated thereafter. The metabolic profiles of mice were analyzed during 4 weeks of treatment, and mice were dissected for histological and gene expression analyses. The direct impacts of MC903 and vitamin D3 were investigated using 3T3-L1 adipocytes and C2C12 myotubes in vitro.ResultsHFD-fed mice showed significant increases in body and epididymal white adipose tissue (eWAT) weights with enlarged adipocytes. They exhibited glucose intolerance, decreased oxygen consumption, and chronic inflammation in eWAT. The transdermal treatment with MC903 significantly ameliorated these metabolic abnormalities in HFD-fed mice without affecting food consumption. In accordance with enhanced energy metabolism, myofiber diameters and the expression of uncoupling protein 3 (UCP3) in the gastrocnemius and soleus muscle were significantly increased in MC903-treated HFD mice. In addition, vitamin D3 and MC903 both suppressed adipogenic differentiation and enhanced lipolysis in 3T3-L1 adipocytes, and increased UCP3 expression in cultured C2C12 myotubes. Furthermore, MC903 increased oxygen consumption and UCP3 knockdown significantly decreased them in C2C12 myotubes.ConclusionsA transdermal treatment with MC903 increased myofiber diameter and energy metabolism and decreased visceral fat accumulation, thereby improving obesity and glucose intolerance in mice.

Dose-Related Regulatory Effect of Raspberry Polyphenolic Extract on Cecal Microbiota Activity, Lipid Metabolism and Inflammation in Rats Fed a Diet Rich in Saturated Fats.

The amount of berry polyphenols required to exert health-promoting effects seems to be difficult to achieve by fresh fruit ingestion, so polyphenol-rich extracts could be considered a dietary alternative. In the present study, laboratory rats were fed high-fat diets supplemented with 0.1 or 0.3% raspberry polyphenols from pomace, with the former dose reflecting the amount of polyphenols consumed with a glass of fresh raspberries. It was hypothesized that beneficial changes in blood and hepatic tissue related to lipid metabolism would accompany both treatments, but the health-promoting effect would be more noticeable with the higher dose of extract. This hypothesis was confirmed, and the high dose of raspberry polyphenols was better than the low dose extract in terms of decreased epididymal white adipose tissue weight, hepatic triglyceride content, PPARγ and SREBP-1c expression in the liver, and plasma IL-6 concentration, as well as increased acetic acid concentration in the cecal digesta. These effects might be partially associated with the enhanced content of ellagitannin and anthocyanin metabolites found in the blood plasma of rats administered the high dose of the extract. The results showed that this extract could be considered a dietary vehicle to provide an amount of raspberry polyphenols that could promote health.

Modulation of PPARα-thermogenesis gut microbiota interactions in obese mice administrated with zingerone.

This study aimed to uncover the potential effects of zingerone (ZIN), one of the bioactive compounds in ginger, on the development of obesity as well as the mechanisms responsible for these effects in C57BL/6J mice fed with a high-fat diet (HFD). Supplementation with 0.2% (wt/wt) zingerone for 16 weeks significantly reduced the final body weight, liver weight, and epididymal white adipose tissue (eWAT) weight without changing the food intake of the mice when compared with the HFD group. The hyperlipidemia of HFD-fed mice was ameliorated after zingerone administration, including decreased plasma triacylglycerol (TG) and total cholesterol (TC) level. The lipid content in liver was lower and the adipocyte size in eWAT and inguinal white adipose tissue (iWAT) was smaller in HFD + ZIN-fed mice compared with HFD group. Zingerone also binds with nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARα) with an optimal docking energy of -7.31 kJ/mol. Uncoupling protein 1 (UCP1), PPAR-γ coactivator-1α (PGC-1α), and PR domain containing 16 (PRDM16), the downstream genes of PPAR which are related to thermogenic function of adipocytes, were significantly increased in both brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) after zingerone administration, in comparison with HFD fed mice. Zingerone intake also restructured the community composition of gut microbiota. The ratio of Firmicutes to Bacteroidetes was decreased, and the relative abundance of Akkermansia_mucinphila was increased. Zingerone can attenuate obesity and related symptoms in HFD-fed mice, probably through the modulation of PPARα-thermogenesis-gut microbiota interactions. © 2022 Society of Chemical Industry.

Dietary High-Dose Biotin Intake Activates Fat Oxidation and Hepatic Carnitine Palmitoyltransferase in Rat

This study investigated the effects of dietary high-dose biotin intake on fat oxidation in rats using respiratory gas analysis, and evaluated fatty-acid oxidation-related enzyme activities and gene expressions in the liver. Five-week-old male Sprague-Dawley rats were fed a control diet and three biotin-supplemented diets (additive biotin concentration: 0.05%, 0.10%, and 0.20% of diet) for 3 wk. In 2 wk, fat oxidation in the 0.20% biotin-supplemented diet group was higher than that in the 0.05% biotin-supplemented diet group; however, the energy expenditure and carbohydrate oxidation were unchanged between the dietary groups. At the end of 3 wk, body weight and epididymal white adipose tissue weight reduced in the 0.20% biotin diet group, and hepatic triglyceride levels tended to decrease. Additionally, increased plasma adiponectin concentration and hepatic mitochondrial carnitine palmitoyltransferase activity as well as decreased hepatic acetyl-CoA carboxylase 2 gene expression were observed in the 0.20% biotin-supplemented diet group compared with those in the control group. These results provide strong evidence that dietary high-dose biotin intake activated fat oxidation due to the increase in hepatic β-oxidation, which may contribute to the decrease in hepatic triglyceride concentration and white adipose tissue weight.

Paternal high-fat diet alters triglyceride metabolism-related gene expression in liver and white adipose tissue of male mouse offspring

Obesity is a major public health problem, and its prevalence is progressively increasing worldwide. In addition, accumulating evidence suggests that diverse nutritional and metabolic disturbances including obesity can be transmitted from parents to offspring via transgenerational epigenetic inheritance. The previous reports have shown that paternal obesity has profound impacts on the development and metabolic health of their progeny. However, little information is available concerning the effects of paternal high-fat diet (HFD) exposure on triglyceride metabolism in the offspring. Therefore, we investigated the effects of paternal HFD on triglyceride metabolism and related gene expression in male mouse offspring. We found that paternal HFD exposure significantly increased the body weight, liver and epididymal white adipose tissue (eWAT) weights, and liver triglyceride content in male offspring, despite consuming control diet. In addition, paternal HFD exposure had induced changes in the mRNA expression of genes involved in lipid and triglyceride metabolism in the liver and eWAT. These findings indicate transgenerational inheritance from the paternal metabolic disturbance of triglyceride and support the effects of paternal lifestyle choices on offspring development and health later in life.

1345-P: Low-Dose Colchicine/Metformin Combination Ameliorates NASH via Regulating AMPK/NRF2/GDF15 Axis in Mice

Nonalcoholic steatohepatitis (NASH) , a complex metabolic disease by multifactorial pathogenesis is demanded multiple pharmacological modes of action for robust treatment strategies. Colchicine has shown efficacy in various clinical settings which inflammation is a key component, however growing evidences suggest that the therapeutic effect of colchicine is multifaceted by intervening in several different pathways involved in inflammation. Here, we investigated the novel therapeutic effects of low-doses of colchicine (LDC) -metformin (LDC-Met) combination to targeting NASH. To induce NASH disorder, C57BL/6J male mice were fed a CDHFD (choline-deficient high fat diet) for 12 weeks, then were orally administrated by LDC-Met with CDHFD for an additional 12 weeks. In CDHFD induced NASH mice models, LDC-Met markedly decreased the NAS and fibrosis score along with reducing serum level of liver enzymes and total cholesterol increased by CDHFD feeding. Consistent with these data, hepatic gene expression of steatosis, fibrosis, inflammation and apoptosis markers increased by CDHFD was noticeably inhibited by LDC-Met. Interestingly, significant increased circulating GDF15 was found in LDC-Met group, which was accompanied by increased hepatic GDF15 expression. Additionally, LDC-Met significantly augmented hepatic phosphorylation of AMPK and NRF2 in CDHFD-fed mice and NLRP3 inflammasome activity were negatively controlled by LDC-Met. Finally, LDC-Met noticeably reduced CDHFD-induced total body weight gain by approximately 20%, along with epididymal white adipose tissue (eWAT) weight reduction. Taken together, we found that the combination of LDC-Met has the best synergistic effect on NASH resolution, suggesting significant implications for potential drug repurposing and new drug development. Moreover, this novel combination elevates circulating levels of GDF15, which is necessary to obtain beneficial effects on energy balance and body weight. Disclosure S.Ham: None. H.Cho: None. C.Jeong: None. J.Youn: None.

Antiobesity Activity of Two Polyherbal Formulations in High-Fat Diet-Induced Obese C57BL/6J Mice.

Obesity and overweight have posed a severe threat to humanity, needing urgent efforts for the development of safe and effective therapeutic interventions. In this research work, we have developed two polyherbal formulations A and B basically consisting of Helianthus tuberosus root powder (also called inulin of synanthrin) along with other herbs for the treatment of obesity. Evaluation of the antioxidant activity of both formulations using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging assays showed good antioxidant potentials. Both formulations A and B showed good antiobesity activity on a diet-induced obesity (DIO) model of mice by effectively lowering the body weight of mice compared to the high-fat diet (HFD) control mice, mainly by reducing the food efficiency ratio (FER). Furthermore, both formulations ameliorated lipoprotein misbalances induced by obesity and thus decreased the atherogenic index. Treatment with both formulations significantly decreased the liver and epididymal white adipose tissue (WAT) weight. This was supported by the improvement in steatosis of the liver and reduced hypertrophy in WAT on histological examination. In addition, formulations A and B have been seen as effective in controlling fasting blood glucose levels probably by alleviating HFD-induced insulin resistance. All of these results collectively suggest that formulations A and B serve as potentially safe and effective herbal interventions to control obesity and its comorbidities.

RIG-I Deficiency Promotes Obesity-Induced Insulin Resistance.

Inflammation and immunity are linked to the onset and development of obesity and metabolic disorders. Pattern recognition receptors (PRRs) are key regulators of inflammation and immunity in response to infection and stress, and they have critical roles in metainflammation. In this study, we investigated whether RIG-I (retinoic acid-inducible gene I)-like receptors were involved in the regulation of obesity-induced metabolic stress in RIG-I knockout (KO) mice fed a high-fat diet (HFD). RIG-I KO mice fed an HFD for 12 weeks showed greater body weight gain, higher fat composition, lower lean body mass, and higher epididymal white adipose tissue (eWAT) weight than WT mice fed HFD. In contrast, body weight gain, fat, and lean mass compositions, and eWAT weight of MDA5 (melanoma differentiation-associated protein 5) KO mice fed HFD were similar to those of WT mice fed a normal diet. RIG-I KO mice fed HFD exhibited more severely impaired glucose tolerance and higher HOMA-IR values than WT mice fed HFD. IFN-β expression induced by ER stress inducers, tunicamycin and thapsigargin, was abolished in RIG-I-deficient hepatocytes and macrophages, showing that RIG-I is required for ER stress-induced IFN-β expression. Our results show that RIG-I deficiency promotes obesity and insulin resistance induced by a high-fat diet, presenting a novel role of RIG-I in the development of obesity and metabolic disorders.

Colonic Medium-Chain Fatty Acids Act as a Source of Energy and for Colon Maintenance but Are Not Utilized to Acylate Ghrelin.

The capacity of microbiota to produce medium-chain fatty acids (MCFA) and related consequences for the gastrointestinal (GI) tract have never been reported before. We verified the impact of nutrition-related factors on fatty acid (FAs) production and found that caloric restriction decreased levels of most of MCFAs in the mouse cecum, whereas overnight fasting reduced the levels of acetate and butyrate but increased propionate and laurate. A diet high in soluble fibre boosted the production of short-chain fatty acids (SCFA) and caproate whereas a high-cellulose diet did not have an effect or decreased the levels of some of the FAs. Rectal infusion of caprylate resulted in its rapid metabolism for energy production. Repeated 10-day MCFA infusion impacted epididymal white adipose tissue (eWAT) weight and lipid accumulation. Repeated infusion of caprylate rectally tended to increase the concentration of active ghrelin in mice plasma; however, this increase was not statistically significant. In Caco-2 cells, caprylate increased the expression of Fabp2, Pdk4, Tlr3, and Gpr40 genes as well as counteracted TNFα-triggered downregulation of Pparγ, Occludin, and Zonulin mRNA expression. In conclusion, we show that colonic MCFAs can be rapidly utilized as a source of energy or stored as a lipid supply. Further, locally produced caprylate may impact metabolism and inflammatory parameters in the colon.

Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice

Doxepin is commonly prescribed for depression and anxiety treatment. Doxepin-related disruptions to metabolism and renal/hepatic adverse effects remain unclear; thus, the underlying mechanism of action warrants further research. Here, we investigated how doxepin affects lipid change, glucose homeostasis, chromium (Cr) distribution, renal impairment, liver damage, and fatty liver scores in C57BL6/J mice subjected to a high-fat diet and 5 mg/kg/day doxepin treatment for eight weeks. We noted that the treated mice had higher body, kidney, liver, retroperitoneal, and epididymal white adipose tissue weights; serum and liver triglyceride, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and creatinine levels; daily food efficiency; and liver lipid regulation marker expression. They also demonstrated exacerbated insulin resistance and glucose intolerance with lower Akt phosphorylation, GLUT4 expression, and renal damage as well as higher reactive oxygen species and interleukin 1 and lower catalase, superoxide dismutase, and glutathione peroxidase levels. The treated mice had a net-negative Cr balance due to increased urinary excretion, leading to Cr mobilization, delaying hyperglycemia recovery. Furthermore, they had considerably increased fatty liver scores, paralleling increases in adiponectin, FASN, PNPLA3, FABP4 mRNA, and SREBP1 mRNA levels. In conclusion, doxepin administration potentially worsens renal injury, nonalcoholic fatty liver disease, and diabetes.

Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice

Obesity is a large and growing global health problem with few effective therapies. The present study investigated metabolic and physiological benefits of nicotinamide N-methyltransferase inhibitor (NNMTi) treatment combined with a lean diet substitution in diet-induced obese mice. NNMTi treatment combined with lean diet substitution accelerated and improved body weight and fat loss, increased whole-body lean mass to body weight ratio, reduced liver and epididymal white adipose tissue weights, decreased liver adiposity, and improved hepatic steatosis, relative to a lean diet substitution alone. Importantly, combined lean diet and NNMTi treatment normalized body composition and liver adiposity parameters to levels observed in age-matched lean diet control mice. NNMTi treatment produced a unique metabolomic signature in adipose tissue, with predominant increases in ketogenic amino acid abundance and alterations to metabolites linked to energy metabolic pathways. Taken together, NNMTi treatment’s modulation of body weight, adiposity, liver physiology, and the adipose tissue metabolome strongly support it as a promising therapeutic for obesity and obesity-driven comorbidities.

Antiobesity and antidiabetic effects of the dairy bacterium Propionibacterium freudenreichii MJ2 in high-fat diet-induced obese mice by modulating lipid metabolism

Obesity can cause chronic metabolic disorders such as type 2 diabetes, hyperlipidemia, and nonalcoholic fatty liver diseases. The aim of this study was to investigate the antiobesity and antidiabetic effects of the dairy bacterium P. freudenreichii MJ2 isolated from raw milk using 3T3-L1 cells and high-fat diet (HFD)-induced obese mice. Lipid accumulation and the expression levels of genes related to lipid metabolism, such as preadipocytic gene (Pref-1), adipogenic genes (PPARγ and C/EBPα), and lipogenic genes (FAS, SCD-1, and ACC), significantly decreased in heat-killed P. freudenreichii MJ2 (hkMJ2)-treated adipocytes. Live P. freudenreichii MJ2 (MJ2), hkMJ2, and Lactobacillus plantarum (LP) decreased body weight gain in HFD-induced obese mice compared with the model group. The liver and epididymal white adipose tissue weights in the MJ2-, hkMJ2- and LP-treated groups were significantly lower than those in the model group. The expression levels of genes and proteins related to adipogenesis and lipogenesis significantly decreased and lipolysis (HSL and ATGL) increased in the MJ2-, hkMJ2-, and LP-treated groups. The expression levels of genes related to fatty acid β-oxidation (CPT-1α and ACOX1) increased in the MJ2-, hkMJ2-, and LP-treated groups. In addition, blood glucose and fasting insulin levels in the MJ2- and hkMJ2-treated groups decreased compared with those in the model group. P. freudenreichii MJ2 ameliorate insulin resistance by obesity. In conclusion, both MJ2 and hkMJ2 alleviate obesity and metabolic syndrome.

Evaluation of the ameliorative effect of Spirulina (Arthrospira platensis) supplementation on parameters relating to lead poisoning and obesity in C57BL/6J mice

• Oral exposure of Spirulina to C57BL/6J mice with lead acetate and high-fat diet. • Lead-related anemia was normalized and hematocrit and ALAD activity were recovered. • Decrease of epididymal white adipose tissue and increase of HDL-C by Spirulina. • Mitigative effects of Spirulina on lead poisoning and obesity were suggested. The current study aimed to validate the possible ameliorative effects of Spirulina ( Arthrospira platensis ) on lead poisoning and obesity using C57BL/6J mice. After a treatment period, we performed metal analyses, as well as hematocrit and plasma biochemical parameter measurements, and assayed oxidative stress markers and erythrocyte δ-aminolevulinic acid dehydratase (ALAD) activity. Our results highlighted the effectiveness of Spirulina in improving anemia status with the normalization of hematocrit levels and ALAD activity ratios, even in mice that exhibited obesity in addition to lead poisoning. Spirulina treatment also decreased epididymal white adipose tissue weight and increased plasma high-density lipoprotein levels, which are normally reduced after lead exposure. However, most of the studied plasma biochemical parameters and oxidative stress markers did not show large changes after treatment, likely because of the short duration of treatment. Further studies with longer-term exposures are required to validate the usefulness of Spirulina suggested in the present study.

Dietary Administration of 2-Deoxy-D-Glucose Reduces High Fat Diet Induced Obesity and meta-inflammation in Mice

Obesity is a major risk factor for type 2 diabetes, NAFLD, chronic diseases and cancer. Insulin resistance, oxidative stress, high ectopic lipid levels and meta-inflammation are the mechanisms proposed to play a leading role in the morbidity associated with obesity. Energy restriction mimetics (ERMAs) has also been shown earlier to reduce the scale and the severity of these disorders by mimicking the physiological effects of the Energy Restriction. In present study we propose that the use of 2-DG as ERMA can be effective in regulating the High Fat Diet (HFD) induced obesity. Effect of 2-DG (0.4% w/v in drinking water) on the HFD and Insulin Resistance (IR). HFD induced change in body weight, adipose tissue mass, and ectopic lipid levels was assessed as the measure of obesity.IR and glucose levels were also estimated to evaluate the effect of 2-DG on the insulin sensitivity in HFD mice. 2-DG significantly altered HFD induced increase in the mice body weight, epididymal White Adipose Tissue (WAT) and liver weight. 2-DG fed mice also showed reduced lipid levels in serum and liver. Furthermore, 2-DG also reduced the oxidative damage in the liver with concomitant increase in enzymatic (SOD and Catalase) and non-enzymatic (reduced Glutathione) antioxidant levels. 2-DG fed mice also showed reduced levels of Leptin, IL-6 and TGF-β which are early drivers of the etiology of the metabolic diseases. Our results suggest that 2-DG as ERMA can prevent obesity and etiology of associated disorders. However, more relevant models are needed to further strengthen these observation

Abstract 17023: Adipose Tissue Specific Temporal Deletion of Ager Induces Weight Loss in Diet Induced Obese Mice and Improves Glucose Homeostasis

Introduction: The incidence of obesity and its comorbidities is increasing at an alarming rate in US and around the globe. Our previous studies showed that the receptor for advanced glycation end products (RAGE) and its ligands contribute to the pathogenesis of obesity and insulin resistance (IR), as global Ager (gene encoding RAGE) and adipocyte-specific Ager- deleted mice fed a high fat diet (HFD) showed protection from weight gain and IR. However, the role of Ager deletion in mice with established obesity, switched to low fat diet has not been tested. We hypothesize that temporal adipocyte-specific deletion of Ager in obese mice could enhance weight loss and improves glucose homeostasis. Methods: Mice with conditional adipocyte-specific Ager deletion were generated by breeding Ager flox/flox mice with AdipoQ ERT2 Cre recombinase mice resulting in Ager flox/flox / AdipoQ ERT2 Cre (+) and Cre (-) animals. Mice were fed HFD (60% kcal/fat) for 20 weeks starting at 8 weeks of age to establish obesity and were then treated with tamoxifen (TAM) (75 mg/kg per day x 3 alternative days) to induce deletion of Ager . After 4 weeks of TAM treatment, mice were switched to standard chow for 7 weeks and body weight was monitored regularly. Fasting glucose, insulin and glucose tolerance was measured. Results: After 7 weeks of switching to standard chow following TAM, Cre (+) lost significantly more body weight whereas Cre (-) mice showed no significant weight loss over 7 weeks. Furthermore, Cre (+) mice exhibited significantly higher food intake, lower fasting glucose, lower epididymal and inguinal white adipose tissue weights, and improved glucose and insulin tolerance compared to Cre (-) mice. Conclusions: Temporal adipocyte-specific deletion of Ager in mice with established obesity promotes weight loss and improves glucose homeostasis. RAGE may act as a novel therapeutic target in obesity.