Fat Pad Weight Research Articles

Lipocalin 2 deficiency-induced gut microbiota dysbiosis evokes metabolic syndrome in aged mice.

Lipocalin 2 (Lcn2) is a multifunctional innate immune protein that limits microbial overgrowth. Our previous study demonstrated that the gut microbiota directly induces intestinal Lcn2 production, and Lcn2-deficient (Lcn2-/-) mice exhibit gut dysbiosis. Coincidentally, gut dysbiosis is associated with metabolic syndrome pathogenesis, and elevated Lcn2 levels has been considered a potential clinical biomarker of metabolic syndrome. Yet whether Lcn2 mitigates or exacerbates metabolic syndrome remains inconclusive. Our objective was to determine whether Lcn2 deficiency-induced compositional changes in gut microbiota contribute to gain in adiposity in aged mice. Utilizing Lcn2-/- mice and their wild-type (WT) littermates, we measured metabolic markers, including fasting blood glucose, serum lipids, fat pad weight, and insulin resistance at ages 3, 6, and 9 mo old. Relative to WT mice, aged Lcn2-/- mice exhibited a gain in adiposity associated with numerous features of metabolic syndrome, including insulin resistance and dyslipidemia. Surprisingly, supplementation with a high-fat diet did not further aggravate metabolic syndrome that spontaneously occurs in Lcn2-/- mice by 6 mo of age. Interestingly, chow-fed Lcn2-/- mice displayed marked differences in the bacterial abundance and metabolomic profile of the gut microbiota compared with WT mice. Overall, our results demonstrate that Lcn2 is essential to maintain metabolic and gut microbiotal homeostasis, where deficiency induces spontaneous delayed onset of metabolic syndrome.

Whole Egg Consumption Decreases Cumulative Weight Gain in Diet-Induced Obese Rats

Whole egg (WE) consumption has been demonstrated to attenuate body weight (BW) gain and adiposity in genetic animal models of type 2 diabetes (T2D). This finding was accompanied by increased food consumption. This study aimed to examine the effects of long-term WE intake on BW gain, fat distribution, and food intake in a rat model of diet-induced obesity (DIO). Male Sprague Dawley rats (n=24) were obtained at 5 wk of age and were randomly weight-matched across 1 of 4 dietary intervention groups (6 rats per group): a casein-based diet (CAS), a high-fat high-sucrose CAS diet (HFHS CAS), a whole egg-based diet (EGG), or a high-fat high-sucrose EGG diet (HFHS EGG). All diets provided 20% (w/w) protein and were provided for 33 wk. HFHS diets provided ∼61% of kilocalories from fat and 10% from sucrose. Daily weight gain and food intake were recorded, biochemical parameters were measured via ELISA, and epididymal fat pad weights were recorded at the end of the study. At 33 wk, cumulative BW gain in DIO rats fed HFHS EGG resulted in 23% lower weight gain compared with DIO rats fed HFHS CAS (P <0.0001), but no significant differences in BW gain were observed between the HFHS EGG group and the control EGG and CAS groups (P=0.71 and P=0.61, respectively). Relative food intake (grams per kilogram BW) was 23% lower (P<0.0001) in rats fed HFHS CAS compared with CAS, whereas there was no difference in food intake within the EGG dietary groups. DIO rats fed HFHS EGG exhibited a 22% decrease in epididymal fat weight compared with their counterparts fed the HFHS CAS. Our data demonstrate that consumption of a WE-based diet reduced BW gain and visceral fat in the DIO rat, similar to our previous findings in a genetic rat model with T2D.

Inhibitory Effect of Betanin From Hylocereus ocamponis Against Steatohepatitis in Mice Fed a High-Fat Diet

Betanin is a phytocompound whose effect in steatohepatitis has not yet been tested. Betanin was extracted from the fruits of Hylocereus ocamponis, and its effects were evaluated in a mice model for non-alcoholic fatty liver disease. Six-week-old male BALB/c mice fed with a high-fat diet received 9.6 mg of betanin per day during 40 days. Body, liver, and epididymal fat pad weights and the levels of blood serum total cholesterol, triglycerides, high-density lipoproteins, alanine aminotransferase, blood nitrogen urea, creatinine, and total antioxidant capacity were measured. Hepatosteatosis and inflammatory infiltration were categorized, and the relative cell area of hepatocytes was determined. Betanin inhibited the inflammatory infiltration of the liver ( P = 4.000 × 10−6) and the necrosis of hepatocytes ( P = 9.634 × 10−7); it also produced a predominance of microvesicular steatosis ( P = 9.634 × 10−7), decreased epididymal fat pad weight ( P = 8.250 × 10−4), and increased blood serum total cholesterol ( P = 0.011). Betanin is a promising compound for fatty liver, steatohepatitis, and chronic liver disease.

5-Hydroxytryptophan Suppresses the Abdominal Fat Deposit and Is Beneficial to the Intestinal Immune Function in Broilers.

BackgroundSerotonin (5-HT), a monoaminergic neurotransmitter, involves in the regulation of many physiological functions. In the present study, the effects of 5-hydroxytryptophan (5-HTP), the precursor of 5-HT, on lipid metabolism and intestinal immune function in broiler chickens were investigated in chickens.MethodsTwo hundred broilers were divided randomly into two groups and fed separately with a corn-soybean basal diet (CD) or the basal diet supplemented with 0.2% 5-HTP.ResultsThe results showed that 5-HTP reduced (P < 0.05) feed intake and the abdominal fat pad weight. 5-HTP treatment tended to upregulate the mRNA level of adiponectin receptor 1 (ADP1R) and ADP2R in abdominal fat but had no significant influence on their protein levels (P > 0.05). In 5-HTP-chickens, lipopolysaccharide exposure decreased secretory immunoglobulin A (sIgA) concentrations in serum and the duodenal contents. Expression of mRNA encoding interleukin (IL), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β) decreased after 5-HTP treatment; however, LPS increased expression significantly in 5-HTP-treated chickens compared with CD chickens. In 5-HTP-chickens, the phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) were reduced, but the phosphorylation of ribosomal p70S6 kinase (p70S6K) was increased in the duodenum.ConclusionIn summary, the result suggests that dietary 5-HTP supplementation reduces accumulation of abdominal fat and is beneficial to intestinal immune function.

The high-fructose intake of dams during pregnancy and lactation exerts sex-specific effects on adult rat offspring metabolism.

Experimental studies have demonstrated the effects of maternal fructose consumption during pregnancy and lactation on metabolic alterations in their offspring, especially male offspring. However, few studies have focused on female offspring after providing fructose in food to dam rats. Here, we studied whether offspring of both sexes were differentially affected by a maternal high-fructose diet (HFD). For this purpose, Sprague-Dawley rats were fed during pregnancy and lactation with a standard diet (SD) or a HFD (50% w/w). After weaning, offspring were fed an SD; 3 days later, dams were sacrificed, and their offspring were sacrificed on postnatal day 90. Body weight (BW), food and water intake (only for dams), and various biomarkers of metabolic syndrome were measured. When compared to the SD-fed dams, HFD-fed dams had a reduction in BW and food and water intake. Conversely, adiposity, liver weight, liver lipids, and plasma levels of glucose, insulin, cholesterol, triglycerides, and uric acid were increased in HFD-fed dams. Moreover, the BW, food consumption, weight of retroperitoneal fat pads, and liver lipids increased in female and male offspring of HFD-fed dams. Interestingly, the pups of HFD-fed mothers showed increased levels of leptin and insulin resistance and decreased levels of adiponectin which were more pronounced in male offspring than in female offspring. In contrast, a higher increase in BW was shown earlier in female offspring. Thus, high-fructose consumption by dams during pregnancy and lactation led to sex-specific developmental programming of the metabolic syndrome phenotype in adult offspring.

Prebiotics Must Achieve a Threshold of Increase in Gut Probiotic Bacteria to Impart Beneficial Health Effects on the Host

Abstract Objectives Prebiotic dietary fibers are dietary fibers that] are highly fermented in the large intestine, produce beneficial changes in the gut microbiome, and impart a health benefit to the host. Using reactive extrusion, we have synthesized a novel dietary fiber that is an oligosaccharide of polymerized lactose, which we term polylactose. Here we report on two studies feeding polylactose to rats to determine its prebiotic potential. Methods In Exp. 1, the polylactose preparation contained 51% dietary fiber, 20% free lactose, 5% glucose, and 24% other materials. Rats were fed high fat diets containing 9% total dietary fiber, including cellulose (control, CE, 9%), polylactose (PL, 6%), polydextrose (PD, 6%), and fructooligosaccharide (FOS, 6%). In Exp. 2, the polylactose preparation contained 75% dietary fiber, 9% lactose, 3% glucose, and 13% other materials. Rats were again fed high fat diets containing 9% total dietary fiber, including CE (9%), polylactose (6% or 3%), PD (6%), and galactooligosaccharide (GOS, 6%). In both experiments, rats were fed for 10 weeks, then cecums (empty), cecal contents, livers, and epididymal fat pads were collected. In addition, body composition was determined by MRI. Results In both experiments, final body weight and daily energy intake did not differ among the groups. In Exp. 1, feeding PL greatly increased cecum weight (an indicator of fermentation), cecal Bifidobacterium and Lactobacillus species abundance, increased cecal acetate and propionate, and reduced liver lipids and fat pad weight, compared to the CE group. While PD and FOS increased probiotic species and short chain fatty acids slightly (compared to CE), this was not to the same extent as PL and did not reduce fatty liver and adiposity. In Exp. 2, 6% PL increased cecum weight relative to 3% PF, PD and GOS, all of which were greater than CE. The cecal microbiome was similar among PL (both 3 and 6%), PD, and GOS, all of which differed from CE and were similar to PD and FOS from Exp. 1. Liver lipids, fat pad weight, and body composition did not differ among any of the groups. Conclusions The prebiotic activity of polylactose differed depending on the preparation, for unknown reasons. However, our results suggest there is a threshold of probiotic bacteria abundance that must be attained before beneficial effects are imparted on the host by prebiotics. Funding Sources Midwest Dairy Association.

Pharmacological Inhibition of Soluble Epoxide Hydrolase by t-TUCB Improves Brown Adipose Tissue Activities in Diet-Induced Obesity

Abstract Objectives Brown adipose tissue (BAT), responsible for energy expenditure through nonshivering thermogenesis, has emerged as a novel target for obesity treatment and prevention. Soluble epoxide hydrolase (sEH), encoded by Ephx2 gene, is a cytosolic enzyme that converts epoxy fatty acids (EpFAs) that are produced by cytochrome P-450 enzymes from polyunsaturated fatty acids into less active diols. Pharmacological inhibitors of sEH, such as trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido] cyclohexyloxy} benzoic acid (t-TUCB), have been shown to be beneficial for chronic diseases by inhibiting the degradation of EpFAs. We have previously shown that t-TUCB dose-dependently promotes brown adipogenesis in vitro. This study investigated the therapeutic effects of t-TUCB on BAT activation in diet-induced obese mice. Methods Male C57BL6/J mice were fed a high-fat diet (60% kcal from fat) for 8 weeks followed by random assignment into either the control or t-TUCB group (n = 10 per group) to receive either the vehicle control or t-TUCB (3 mg/kg/day) via osmotic minipump delivery at the subcutaneous area near the interscapular BAT for 6 weeks. Bodyweight and food intake, glucose and insulin tolerance tests, cold tolerance tests, and indirect calorimetry were measured before the mice were euthanized for further biochemical analysis. Results sEH inhibition by t-TUCB in the obese mice did not change body weight, fat pad weight, food intake, fasting blood glucose, glucose and insulin tolerance, or cold tolerance, but significantly decreased blood triglyceride levels and increased heat production during both day and night. Moreover, t-TUCB significantly increased protein expression of brown marker gene PGC-1alpha and lipid droplet-associated protein perilipin (PLIN), but not uncoupling protein 1 (UCP1), in the interscapular BAT of diet-induced obese mice. Conclusions Our results suggest that sEH pharmacological inhibition may be beneficial for BAT activation by increasing mitochondrial biogenesis and lipolysis in the BAT. Further studies using the sEH inhibitors and/or EpFA generating diets for obesity treatment and prevention are warranted. Funding Sources The work was supported by NIH 1R15DK114790–01A1 (to L.Z.), K99DK100736 and R00DK100736 (to A.B.), R15AT008733 (to S.W.), R35 ES030443 and P42ES004699 (to B.D.H).

Discordant Dose-Dependent Metabolic Effects of Eicosapentanoic Acid in Diet-Induced Obese Mice.

Obesity is a widespread epidemic that increases the risk for several metabolic diseases. Despite several beneficial health effects of eicosapentaenoic acid (C20:5n-3, EPA), previous studies have used very high doses of EPA. In this study, dose-dependent effects of EPA on metabolic outcomes were determined in diet-induced obese mice. We used B6 male mice, fed high-fat diet (HF, 45% kcal fat) or HF diet supplemented with 9, 18, and 36 g/kg of EPA-enriched fish oil for 14 weeks. We conducted metabolic phenotyping during the feeding period, and harvested tissues and blood at termination. Only mice fed 36 g/kg of EPA significantly (p < 0.05) lowered body weight, fat content and epididymal fat pad weight, compared to HF. Both 18 and 36 g/kg doses of EPA significantly increased glucose clearance and insulin sensitivity, compared to HF or 9 g/kg of EPA. Locomotor activity was significantly increased with both 18 and 36 g/kg doses of EPA. Interestingly, all doses of EPA compared to HF, significantly increased energy expenditure and oxygen consumption and significantly reduced serum insulin, leptin, and triglycerides levels. These results demonstrate weight- and adiposity-independent metabolic benefits of EPA, at doses comparable to those currently used to treat hypertriglyceridemia.

Effects of Cabbage-Apple Juice Fermented by Lactobacillus plantarum EM on Lipid Profile Improvement and Obesity Amelioration in Rats.

This study aimed to investigate the potential of cabbage-apple juice, fermented by Lactobacillus plantarum EM isolated from kimchi, to protect against obesity and dyslipidemia that are induced by a high-fat diet in a rat model. Male rats were fed a modified AIN-93M high-fat diet (HFD), the same diet supplemented with non-fermented cabbage-apple juice, or the same diet supplemented with fermented cabbage-apple juice for eight weeks. In the HFD-fermented cabbage- apple juice administered groups the following parameters decreased: body weight, liver and white fat pad weights, serum triglyceride (TG), total cholesterol (TC), LDL-cholesterol, insulin, glucose and leptin levels, TG levels, while HDL-C and adiponectin levels in serum increased as compared with the HFD group. The HFD-fed rats that were supplemented with fermented cabbage-apple juice exhibited significantly lower fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and malic enzyme gene expression levels when compared to the exclusively HFD-fed rats. The anti-obesity and hypolipidemic effects were marginally greater in the fermented juice administered group than in the non-fermented juice administered group. These results suggest that cabbage-apple juice—especially fermented cabbage-apple juice—might have beneficial effects on lipid metabolism dysfunction and obesity-related abnormalities. However, further studies are necessary for analyzing the biochemical regulatory mechanisms of fermented juice for obesity amelioration and lipid metabolic homeostasis.

Threonine, but Not Lysine and Methionine, Reduces Fat Accumulation by Regulating Lipid Metabolism in Obese Mice.

Some amino acids (AAs) have been proven to suppress fat mass and improve insulin sensitivity. However, the impact of important essential AAs, threonine, lysine, and methionine, on obesity has not been clarified. In the present study, after an 8 week period of obesity induction, mice were grouped to receive either a high-fat diet (HFD) or HFD supplemented with lysine, threonine, or methionine (3% in drinking water) for another 10 weeks. The results showed that dietary supplementation with threonine significantly decreased body weight, epididymal and perirenal fat pad weights, serum concentrations of glucose, triacylglycerols, total cholesterol, and LDL-cholesterol compared to the HFD group. HOMA-IR and serum leptin and adiponectin were improved by threonine supplementation. In epididymal adipose tissue, threonine treatment significantly down-regulated the expression levels of lipogenesis and up-regulated expressions of lipolysis compared to the HFD group. Threonine addition stimulated the expression of UCP-1 and related genes in brown adipose tissue. However, lysine or methionine supplementation showed little effect on body weight, WAT weight, serum lipid profiles, and lipid-metabolism-related gene expressions of HFD-fed mice. These findings suggest that threonine inhibited fat mass and improved lipid metabolism of already obese mice, providing a potential agent in treating obesity.

Low-Magnitude High-Frequency Vibration Decreases Body Weight Gain and Increases Muscle Strength by Enhancing the p38 and AMPK Pathways in db/db Mice.

ObjectiveTo evaluate the effect LMHFV on body weight gain, NAFLD and muscle strength and explore effect in mitochondrial biogenesis, AMPKα and p38 pathways.MethodsVibration platform used in this study provides specific whole-body cyclic mechanical stimulation at low magnitude (0.3 g) and high frequency (50 Hz). Diabetic mice (8–9 mice per group) (C57BL/KsJ-m+/+Leprdb) were randomly divided into untreated group (no vibration) and two vibration groups. Lean mice (8 mice) were used as non-diabetic control for both groups. Two diabetic vibration groups received LMHFV every day for 20 min/day and 40 min/day separately.ResultsAfter 8 weeks of treatment, results showed that body weight, liver weight, fat pad weight, glucose level and insulin level were lower in vibration group when compared with the untreated group. The ratio of fat in liver was significantly decreased after vibration treatment. Muscle strength was significantly increased after vibration. Mitochondrial biogenesis-related gene expression was increased in soleus, gastrocnemius and liver. AMPKα mRNA expression level was increased in soleus and gastrocnemius after vibration treatment. p38 and AMPKα mRNA expression level and protein expression level in liver were enhanced with vibration treatment. Moreover, phosphorylation of p38 and AMPKα was enhanced in liver.ConclusionLMHFV applied in our study decreases body weight gain and improves muscle strength and NAFLD in diabetic mice which were partly through improving mitochondrial biogenesis by enhancing p38 and AMPKα pathway.

Female Rats Artificially Selected for Low and High Intrinsic Aerobic Capacity Swap Inflammatory Cascade in Resistance Arteries: Mechanisms of Cyclooxygenase‐Derived Prostanoids

Low‐capacity runner (LCR) rats and high‐capacity runner (HCR) rats are translational models of human physiology as they present a genetic predisposition towards disease and the ultra‐healthy state, respectively. Selected for their low (LCR) and high (HCR) intrinsic aerobic capacity, LCR rats display increased risk of metabolic syndrome and vascular inflammation, whereas HCR rats have decreased risk factors. Cyclooxygenase (COX) is an enzyme that plays a key role in inflammation as well as normal vascular physiology; however, it is unknown if rats with low or high intrinsic capacity present differences in the COX‐induced inflammatory cascade. As obese females display an increased risk to cardiovascular disease compared to males, female LCR rats were used as a model for metabolic syndrome. Therefore, we hypothesized that resistance arteries from female LCR rats would show increased COX activity, while arteries from female HCR rats would show decreased COX activity.Our rat model (female, 18–25 weeks old) study used LCR, HCR, and high‐response trained (HRT) rats as control (n=4/group). HRT rats have a trained aerobic capacity that is higher than LCR but lower than HCR. We quantified cardiac hypertrophy by dividing the left ventricle weight by 26.73 + tibia length (TL)3. Statistics: t‐test: p&lt;0.05: * vs control (HRT); # vs. HCR; &amp; vs. absence of indomethacin (Indo). No differences in fat pad weight between HRT and HCR were observed. However, LCR rats showed increased fat pad weight when compared to HCR [HRT: 1.05±0.2 vs. LCR: 1.57±0.2#; HCR: 0.92±0.1 (g)]. As expected, HCR presented an increased left ventricle weight, indicating physiologic hypertrophy, when compared to LCR. No differences were observed between LCR and control [HRT: 6.84±0.9 vs. LCR: 6.55±0.1#; HCR: 7.73±0.3; 26.73+TL3]. Mesenteric resistance arteries (MRA) were extracted and mounted onto a wire myograph. No significant differences were observed in the acetylcholine and phenylephrine (PE) concentration‐response curves between groups. As expected, arteries from HRT and LCR rats incubated with a nonspecific COX inhibitor [indomethacin (Indo), 10 μM] presented a significant decrease in contraction. Interestingly, indomethacin did not alter or decrease phenylephrine‐induced contraction in arteries from HCR [PE: Emax%: HRT: control 93±3 vs. Indo 3±0.6&amp;; LCR: control 62±17 vs. Indo 2±0.7&amp;; HCR: control 94±6 vs. Indo 80±9] (Fig 1). Overall, these data reveal a new, dichotomous mechanism for vascular inflammation and contractility in LCR and HCR rats. Specifically, we observed that arteries from female rats born with high aerobic capacity are unresponsive to COX inhibition during phenylephrine contraction, perhaps to maintain the high vascular flow needed for their higher exercise metabolism. This may be caused by a swap mechanism from a normal inflammatory state to a higher inflammatory‐resolution state. Our study constitutes the basis for the discovery of new therapeutic targets for vascular inflammation in people with high aerobic capacity.Support or Funding InformationThis work was supported by National Institutes of Health (NIH) (NIH: R00GM118885)Concentration‐response curves to phenylephrine, with and without indomethacin (10 uM), in mesenteric resistance arteries (MRA) from (A) HRT, (B) LCR, and (C) HCR rats. (D) The average maximum response (Emax) of MRA to phenylephrine, with and without indomethacin (10 uM). T‐test: &amp; vs. absence of Indo p&lt;0.05.Figure 1

Reduced responsiveness of bone marrow hematopoietic cells to sympathetic activation is protective against high fat diet‐induced obesity and gut dysbiosis

INTRODUCTIONGenetic ablation of beta 1 and 2 receptors in the bone marrow (BM) results in mild immunosuppression and beneficial shifts in the gut microbiota. Considering the role of sympathetic activity, inflammation and gut dysbiosis in obesity, we hypothesized that reduction of BM responsiveness to sympathetic activation will dampen the deleterious effects of high‐fat diet (HFD) via protective host‐microbiota interaction.METHODSChimera BM mice were generated by reconstituting sub lethally‐irradiated C57BL/6J mice with whole BM cells from either the beta‐adrenergic 1/2 receptor knock down (BM C57‐Adrb1.b2 KD) or C57BL/6J mice (BM C57‐C57). Circulating T cells, monocytes, and macrophages were measured at baseline. Both groups of mice were randomized to either control (ND, 10% kcal fat, n=4/5 per group) or high‐fat diet (HFD, 60% kcal fat, n=5/6 per group) ad libitum for two weeks. Body weights and food intake were monitored throughout the study. Magnetic resonance imaging was used to determine body composition and fat to muscle ratio. Visceral fat pads were weighed, and relative abundance of major gut bacterial phyla were determined using qPCR at endpoint.RESULTSBM C57‐Adrb1.b2 KD mice were protected from obesity‐related outcomes such as increased total weight gain, total body fat to muscle ratio, and visceral fat pad weight, all of which were all present in the BM C57‐C57 mice on HFD (P&lt;0.05 vs ND). Interestingly, no difference in the food intake was observed between the experimental groups. BM C57‐Adrb1.b2 KD chimera also presented with lower circulating inflammatory Ly6C+ monocytes compared to the BM C57‐C57 chimera mice (p&lt;0.05), prior to HFD feeding. Notably, BM C57‐Adrb1.b2 KD chimera were also protected from HFD‐dependent alterations in major bacterial phyla such as Firmicutes and Actinobacteria, compared to the BM C57‐C57 chimera in which the same phyla were significantly altered by HFD (P&lt;0.05 vs ND).CONCLUSIONThese data demonstrate that the BM C57‐Adrb1.b2 KD mouse, characterized by reduced responsiveness of BM hematopoietic cells to sympathetic activation, is protected against obesity possibly via mechanisms involving reduction in pro‐inflammatory monocytes and protection against alteration in the specific gut bacterial phyla.

Dose‐Dependent Anti‐Inflammatory and Metabolic Effects of Eicosapentaenoic Acid in Diet‐Induced Obese Mice

Obesity is a widespread epidemic that increases the risk for several metabolic diseases such as diabetes and cardiovascular diseases. Long‐chain omega‐3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) possess anti‐inflammatory and potent triglyceride‐lowering properties at high doses (4–6 g/day). However, whether lower doses are effective in reducing metabolic alterations associated with obesity has not been investigated. The objective of this study is to determine dose‐dependent effects of EPA in diet‐induced obese mice. We used B6 male mice fed for 14 weeks a high‐fat diet (HF, 45% kcal fat) or HF diet supplemented with 36, 18, or 9 g/kg of AlaskOmega EPA‐enriched fish oil (800mg EPA/g fish oil), kindly provided by Organic Technologies. We conducted metabolic phenotyping during the feeding period, and harvested tissues and blood at termination. There were no differences in food intake across the four treatment groups. Only 36 g/kg of EPA significantly lowered body weight, fat content and epididymal fat pad weight (P&lt;0.05), compared to HF. However, EPA at both 18 and 36 g/kg doses significantly increased glucose clearance and insulin sensitivity (P&lt;0.05), compared to mice fed HF or 9 g/kg of EPA. Locomotor activity was significantly increased (P&lt;0.05) in mice fed EPA 36 and 18 g/kg compared to other groups. Interestingly, compared to HF with all doses of EPA, energy expenditure and oxygen consumption were significantly increased (P&lt;0.05); while serum insulin and leptin levels were significantly decreased (p&lt;0.05). These results validate weight‐ and adiposity‐ independent metabolic benefits of EPA in obesity and demonstrate that doses of EPA comparable to those currently used to treat hypertriglyceridemia (18g/kg mouse diet, ~5g/d human diet) confer several metabolic benefits.Support or Funding InformationUSDA NIFA Postdoctoral Fellowship Grant # 2017‐07139

Preventive Effect of Fermented Chestnut Inner Shell Extract on Obesity-Induced Hepatic Steatosis.

This study aimed to investigate the effects of the gallic acid-enriched fermented chestnut inner shell extract (FCCE) by Saccharomyces cerevisiae on a high fat diet (HFD)-induced obesity and hepatic steatosis in vivo mouse model. Mice feeding FCCE exhibited reduced body weight gain compared to those in the HFD-fed group, and showed lower abdominal fat pad weight including epididymal, retroperitoneal, and mesenteric adipose tissue. Further, FCCE administration decreased adipocyte size by suppressing adipogenic factors such as peroxisome proliferator activated receptor γ and CCAAT/ enhancer-binding protein α, and lipogenic factors such as sterol regulatory element-binding protein-1c, fatty acid synthase, and stearoyl CoA desaturase-1. Moreover, FCCE decreased levels of lipids in serum and liver as well as serum alanine aminotransferase and aspartate aminotransferase levels, markers of liver injury. Histological observations of the liver showed that FCCE significantly attenuated HFD-induced hepatic steatosis. The effect of FCCE on hepatic lipid regulatory factors may be partly associated with adenosine monophosphate-activated protein kinase activation. These results suggest that gallic acid-enriched FCCE has potential to be a promising functional food for prevention of obesity and obesity-related fatty liver disease.

Are Bisphosphonates Associated with Adverse Metabolic and Cognitive Effects? A Study in Intact Rats and Rats Fed High-Fat High-Fructose Diet.

Osteocalcin, known as a bone gla protein, is considered a regulator of energy metabolism and behavior in its undercarboxylated form (ucOC). Antiresorptive drugs, such as alendronate, reduce serum level of ucOC. The purpose of the current study was to verify if alendronate might impact on energy metabolism and animal behavior by reducing ucOC level and to find out if the presence of metabolic alterations would further worsen these potential adverse effects. Four groups of male Wistar rats (12 per group) were used: a control group, a group receiving high-fat high-fructose diet (HFHF), a group treated with alendronate, and a group receiving alendronate and HFHF. Alendronate was administered subcutaneously in a dose of 50 mcg/kg thrice weekly. Study duration was 15weeks. Animals were tested for locomotion, anxiety and spatial memory. Glucose and insulin tolerance tests evaluated the glucose metabolism. Visceral obesity was assessed by the weight of right retroperitoneal fat pads. Concentration of ucOC was measured in the serum. Alendronate reduced serum ucOC concentration, increased fasting blood glucose level, and worsened insulin sensitivity. It did not increase visceral adiposity. Fat index was negatively correlated with ucOC in all animals and in the alendronate-treated rats. Alendronate worsened spatial memory of the animals and ucOC levels correlated positively with their cognitive performance.

Muscle Hyperplasia in Japanese Quail by Single Amino Acid Deletion in MSTN Propeptide.

Mutation in myostatin (MSTN), a negative regulator of muscle growth in skeletal muscle, resulted in increased muscle mass in mammals and fishes. However, MSTN mutation in avian species has not been reported. The objective of this study was to generate MSTN mutation in quail and investigate the effect of MSTN mutation in avian muscle growth. Recently, a new targeted gene knockout approach for the avian species has been developed using an adenoviral CRISPR/Cas9 system. By injecting the recombinant adenovirus containing CRISPR/Cas9 into the quail blastoderm, potential germline chimeras were generated and offspring with three base-pair deletion in the targeted region of the MSTN gene was identified. This non-frameshift mutation in MSTN resulted in deletion of cysteine 42 in the MSTN propeptide region and homozygous mutant quail showed significantly increased body weight and muscle mass with muscle hyperplasia compared to heterozygous mutant and wild-type quail. In addition, decreased fat pad weight and increased heart weight were observed in MSTN mutant quail in an age- and sex-dependent manner, respectively. Taken together, these data indicate anti-myogenic function of MSTN in the avian species and the importance of cysteine 42 in regulating MSTN function.

Gochujang prepared using rice and wheat koji partially alleviates high-fat diet-induced obesity in rats.

The aim of this study was to compare whether gochujang products prepared using giant embryo rice koji (rice gochujang, RG) and wheat koji (wheat gochujang, WG) have anti‐obesity effects on rats fed a high‐fat diet (HFD), who served as a model for obesity. The nutritional composition of RG and WG including proximate constituents, amino acid and fatty acid compositions were investigated. Consequently, the secondary fermented metabolites were analyzed in RG and WG by ultrahigh‐performance liquid chromatography and mass spectrometry. Rats were fed a HFD containing 10% RG powder (HFD‐RG) or 10% WG powder (HFD‐WG) for 8 weeks. Body weight gain, weights of liver, epididymal, retroperitoneal, perirenal, and total white fat pads, and levels of serum triglyceride (TG), total cholesterol, low‐density lipoprotein cholesterol, and leptin were lower in all gochujang groups than in the HFD group. Furthermore, RG and WG treatment decreased the hepatic TG content and lipid accumulation and significantly reduced the size of epididymal adipocytes. These effects are probably mediated through inhibition of hepatic fatty acid synthase, acetyl CoA carboxylase, malic enzyme, and adipose tissue lipoprotein lipase activities. The anti‐obesity effect was slightly greater in the HFD‐RG group than in the HFD‐WG group. This effect may be attributed to secondary metabolites, such as capsaicin, genistein, daidzein, soyasaponin, and lysophosphatidylcholines, contained in gochujang prepared using giant embryo rice or wheat koji.

Protein Arginine Methyltransferase 4 Regulates Adipose Tissue Lipolysis in Type 1 Diabetic Mice.

PurposeHypertriglyceridemia is considered to be driven by increased lipolysis in type 1 diabetes mellitus (T1DM). However, information regarding the transcriptional circuitry that governs lipolysis remains incomplete in T1DM. Protein arginine methyltransferase 4 (PRMT4), a transcriptional coactivation factor, promotes autophagy and may play an important role in lipolysis. We wonder whether activated lipolysis in T1DM is regulated by PRMT4.Materials and MethodsRecombinant adeno-associated virus was adopted to overexpress PRMT4 in adipose tissue of mice. Streptozotocin (150 mg/kg) was injected intraperitoneally into mice to induce T1DM. Plasma insulin, triglycerides, free fatty acids (FFAs) levels were determined using commercial assay kits. Differentiated adipocytes were applied to verify the regulation of PRMT4 on lipolysis.ResultsElevated serum triglycerides and FFAs were observed in PRMT4-overexpressed T1DM mice. We also observed that PRMT4 over-expression induced the decrease of fat pads weights and adipocyte sizes. Moreover, expression levels of lipolysis-related molecules, including ATGL, HSL, and MAGL, and HSL phosphorylation levels were increased in PRMT4-overexpressed mice when compared to those of control mice. In vitro, PRMT4 promoted FFAs release and activated HSL phosphorylation, whereas PRMT4 knockdown inhibited these processes.ConclusionPRMT4 promotes lipolysis and increases serum triglyceride in T1DM.

Using crystalline amino acids to supplement broiler chicken requirements in reduced protein diets

Reducing dietary CP can reduce N pollution. Much research has been reported in corn-based diets; however, the amino acid (AA) profiles of wheat-based diets differ. Poor performance as a result of reduced protein (RP) has been overcome in corn-based diets with essential AA and glycine (Gly) supplementation. The current study examined RP levels and Gly in wheat-based diets. An industry standard protein (SP) diet plus 3 RP diets with and without Gly supplementation, to match the SP treatment at 0.713 and 0.648% digestible Gly for the grower and finisher periods respectively, were fed to male broilers from day 10 of age. Grower CP included 22.5, 20.6, 18.3, and 17.7% (days 10–21) and finisher CP included 19.7, 17.8, 16.2, and 15.5% (days 21–35). Performance, meat yield, N efficiency, water intake, and apparent ileal digestibility of N and AA were measured. No difference in body weight gain (BWG), feed intake, or feed conversion ratio (FCR) were observed at 20% CP compared to the SP treatment. However, further reducing protein reduced BWG (P < 0.001), feed intake (P < 0.001), and increased FCR (P < 0.001). Supplementation of 0.713% Gly in the grower period increased BWG (P < 0.001) and reduced FCR (P < 0.001). Relative meat yield was not affected by dietary protein, however reducing CP increased relative fat pad weight (P < 0.001). Nitrogen efficiency increased with decreased CP in both grower (R2 = 0.69) and finisher (R2 = 0.80) treatments. Water intake decreased (R2 = 0.83) with decreasing CP intake. Apparent ileal digestibility of AA and N were higher in RP diets (P < 0.05). The benefits of reduced water intake and increased N efficiency and the disadvantages of poor performance and increased body fat in RP corn-based diets have been identified in RP wheat-based diets. Furthermore, at 18.5% CP the supplementation of crystalline AA and Gly can maintain BWG and FCR observed in SP diets.