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1.
Black Raspberry Seed Oil Improves Lipid Metabolism by Inhibiting Lipogenesis and Promoting Fatty‐Acid Oxidation in High‐Fat Diet‐Induced Obese Mice and db/db Mice
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The objective of this study was to evaluate the beneficial effect of α‐linolenic acid‐rich black raspberry seed (BRS) oil on lipid metabolism in high‐fat diet (HFD)‐induced obese and db/db mice. Five‐week‐old C57BL/6 mice were fed diets consisting of 50% calories from lard, 5% from soybean, and 5% from corn oil (HFD), or 50% calories from lard and 10% from BRS oil (HFD + BRS oil diet) for 12 weeks. Six‐week‐old C57BL/KsJ‐db/db mice were fed diets consisting of 16% calories from soybean oil (standard diet), 8% from soybean, and 8% from BRS oil, or 16% from BRS oil for 10 weeks. The BRS oil diets lowered the levels of triacylglycerol, nonesterified fatty acids, and total cholesterol in serum and liver of both of the obese and db/db mice as compared with the HFD and standard diet, respectively. mRNA levels of lipogenesis markers including cluster of differentiation 36, fatty‐acid‐binding protein 1, sterol regulatory element binding protein 1c, fatty‐acid synthase, and solute carrier family 25 member 1 in the liver of the BRS oil groups were lower than those in the liver of the HFD and standard groups in the obese and db/db mice, respectively. On the other hand, fatty‐acid oxidation markers including carnitine palmitoyltransferase 1A, acyl‐CoA dehydrogenase, hydroxylacyl‐CoA dehydrogenase α, and acyl‐CoA oxidase in the liver of the BRS oil groups were higher than those in the liver of the HFD and standard groups in the obese and db/db mice, respectively. Peroxisome proliferator‐activated receptor α mRNA and protein levels increased in the liver and epididymal adipose tissue of the obese and db/db mice fed BRS oil compared with HFD and standard diet, respectively. BRS oil might improve lipid metabolism by inhibiting lipogenesis and promoting fatty‐acid oxidation in HFD‐induced obese and db/db mice. 相似文献
2.
Hepatic and Adipose Tissue Depot-Specific Changes in Lipid Metabolism in Late-Onset Obese (LOB) Rats
Transgenic Late-onset OBesity (LOB) rats slowly develop a male-specific, autosomal dominant, obesity phenotype with a specific
increase in peri-renal white adipose tissue (WAT) depot and preserved insulin sensitivity (Bains et al. in Endocrinology 145:2666–2679,
2004). To better understand the remarkable phenotype of these rats, the lipid metabolism was investigated in male LOB and non-transgenic
(NT) littermates. Total plasma cholesterol (C) levels were normal but total plasma triacylglycerol (TAG) (2.8-fold) and hepatic
TAG content (25%) was elevated in LOB males. Plasma VLDL-C and VLDL-TAG levels were higher while plasma apoB levels were 60%
lower in LOB males. Increased hepatic TAG secretion explained the increased VLDL levels in LOB males. The hepatic gene expression
of FAS, SCD-1, mitochondrial (mt)GPAT, and DGAT2 was up-regulated in both old obese and young non-obese LOB rats. Lipoprotein
lipase (LPL) activity in heart and epididymal white adipose tissue (WAT) was unchanged, while LPL activity was increased in
peri-renal WAT (30%) and decreased in soleus muscle (40%). Moreover, FAS, SCD-1 and DGAT2 gene expression was increased in
peri-renal, but not in epididymal WAT. Basal lipolysis was reduced or unchanged and β-adrenergic stimulated lipolysis was
reduced in WAT from both old obese and young non-obese LOB rats. To summarize, the obese phenotype of LOB male rats is associated
with increased hepatic TAG production and secretion, a shift in LPL activity from skeletal muscle to WAT, reduced lipolytic
response in WAT depots and a specific increase in expression of genes responsible for fatty acid and TAG synthesis in the
peri-renal depot.
F. Frick and R. Hume contributed equally to this work. 相似文献
3.
Cinnamomum camphora Seed Kernel Oil Improves Lipid Metabolism and Enhances β3-Adrenergic Receptor Expression in Diet-Induced Obese Rats
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Jing Fu Cheng Zeng Zheling Zeng Baogui Wang Xuefang Wen Ping Yu Deming Gong 《Lipids》2016,51(6):693-702
The effects of dietary Cinnamomum camphora seed kernel oil (CCSKO) containing medium‐chain triacylglycerols on lipid metabolism and mRNA and protein expression of β‐3 adrenergic receptor in adipose tissue were studied in diet‐induced obese rats. High fat food‐induced obese rats were randomly divided into CCSKO group, Lard group, Soybean oil (SOY) group and naturally restoring group (n = 10). Rats fed with low fat food were used as a normal control group. Significant decreases in body mass and abdominal fat mass/body mass after 12 weeks were found in CCSKO group as compared with Lard and SOY groups (p < 0.05). Levels of blood total cholesterol (TC), triglyceride, free fatty acid, fasting insulin and insulin resistance in the CCSKO group were decreased significantly, and noradrenaline level and insulin sensitivity index in the CCSKO group were significantly higher than other groups. Meanwhile liver TC and triglyceride levels in the CCSKO group were also decreased markedly. Expression levels of β3‐adrenergic receptor mRNA and protein were higher in CCSKO group than in Lard and SOY groups. These results suggest that CCSKO may contribute to reduction of the body fat mass, promote lipid metabolism and up‐regulate β3‐adrenergic receptor expression in high fat diet‐induced obese rats. 相似文献
4.
Kosuke Otani Hiroshi Funada Risa Teranishi Muneyoshi Okada Hideyuki Yamawaki 《International journal of molecular sciences》2022,23(8)
Zucker fatty diabetes mellitus (ZFDM) rats harboring the missense mutation (fa) in a leptin receptor gene have been recently established as a novel animal model of obesity and type 2 diabetes (T2D). Here, we explored changes in cardiovascular dynamics including blood pressure and heart rate (HR) associated with the progression of obesity and T2D, as well as pathological changes in adipose tissue and kidney. There was no significant difference in systolic blood pressure (SBP) in ZFDM-Leprfa/fa (Homo) compared with ZFDM-Leprfa/+ (Hetero) rats, while HR and plasma adrenaline in Homo were significantly lower than Hetero. The mRNA expression of monocyte chemotactic protein-1 in perirenal white adipose tissue (WAT) from Homo was significantly higher than Hetero. Interscapular brown adipose tissue (BAT) in Homo was degenerated and whitened. The plasma blood urea nitrogen in Homo was significantly higher than Hetero. In summary, we demonstrated for the first time that HR and plasma adrenaline concentration but not SBP in Homo decrease with obesity and T2D. In addition, inflammation occurs in WAT from Homo, while whitening occurs in BAT. Further, renal function is impaired in Homo. In the future, ZFDM rats will be useful for investigating metabolic changes associated with the progression of obesity and T2D. 相似文献
5.
The regulation of palmitoyl-CoA chain elongation (PCE) by clofibric acid [2-(4-chlorophenoxy)-2-methylpropionic acid] was
investigated in comparison with stearoyl-CoA desaturase (SCD) in the liver of obese Zucker fa/fa rats. The proportion of oleic
acid in the hepatic lipids of Zucker obese rats is 2.7 times higher than that of lean littermates. The activities of PCE and
SCD in the liver of Zucker obese rats were markedly higher than in lean rats, and the hepatic uptake of 2-deoxyglucose (2-DG)
was also higher in Zucker obese rats compared with lean rats. The increased activities of SCD and PCE in Zucker obese rats
were due to the enhanced expression of mRNA of rELO1. The proportion of oleic acid in the liver was significantly increased
by the administration of clofibric acid to Zucker obese rats, and the hepatic PCE activity and rELO2 mRNA expression, but
not the SCD activity or SCD1 mRNA expression, were increased in response to clofibric acid treatment. By contrast, the activities
of both PCE and SCD and the mRNA expression of SCD1 and rELO2 in the liver were increased by the treatment of Zucker lean
rats with clofibric acid. Multiple regression analysis, which was performed to determine the relationships involving PCE activity,
SCD activity, and the proportion of oleic acid, revealed that the three parameters were significantly correlated and that
the standardized partial regression coefficient of PCE was higher than that of SCD. These results indicate that oleic acid
is synthesized by the concerted action of PCE and SCD and that PCE plays a crucial role in the formation of oleic acid when
Zucker fa/fa rats are given clofibric acid. 相似文献
6.
Marshall B. Elam Matthew A. von Wronski Lauren Cagen Fayanne Thorngate Poonam Kumar Murray Heimberg Henry G. Wilcox 《Lipids》1999,34(8):809-816
We previously demonstrated increased apolipoprotein B (apoB) mRNA editing, elevated levels of mRNA for the catalytic component
of the apoB mRNA editing complex, apobec-1, and increased secretion of the product of the edited mRNA, apoB48, in very low
density lipoproteins (VLDL) in primary cultures of Sprague-Dawley rat hepatocytes following insulin treatment. In order to
determine the effect of in vivo hyperinsulinemia on these processes, we determined apoB mRNA editing, apobec-1 expression, hepatic expression of mRNA for
apoB and other VLDL apoproteins, and the quantity and composition of plasma VLDL in the hyperinsulinemic fatty Zucker rat.
Total apoB mRNA content of the livers of the fatty rats and lean littermates did not differ, however, edited apoB message
coding for hepatic apo B48, and abundance of mRNA for the catalytic subunit of the apoB mRNA editing complex, apobec-1, was
increased by 1.7-and 3.3-fold, respectively, in fatty rats. ApoCIII mRNA abundance was increased in livers of fatty rats as
well, but the abundance of hepatic apoE mRNA in the fatty animal was not different from that of the lean rat. Hepatic apoAI
mRNA abundance was also increased in the fatty rats. Associated with increased apoB mRNA editing, was the 1.7-fold increase
in the fraction of apoB in plasma as apoB48 in fatty rats. VLDL-triglyceride and-apoB in plasma were 15-and 3-fold higher,
respectively, in fatty Zucker rats compared to lean littermates, indicating both enrichment of VLDL with triglycerides and
increased accumulation of VLDL particles. Increased hepatic expression of mRNA for apoCIII and apoAI was associated with increased
content of apoC (and relative depletion of apoE) in VLDL of fatty rats, and plasma apoAI was increased in fatty Zucker rats,
primarily in the HDL fraction. The current study provides further evidence that chronic exposure to high levels of insulin
influences both the quantity of and lipid/apoprotein composition of VLDL in plasma. The increased apoC and decreased apoE
(as well as increased triglyceride) content of VLDL in the fatty Zucker rat observed in the current study may affect VLDL
clearance and therefore may be a factor in the observed accumulation of VLDL in the plasma of the fatty hyperinsulinemic Zucker
rats. 相似文献
7.
Elena Makarova Antonina Kazantseva Anastasia Dubinina Tatiana Jakovleva Natalia Balybina Konstantin Baranov Nadezhda Bazhan 《International journal of molecular sciences》2021,22(19)
The preference for high-calorie foods depends on sex and contributes to obesity development. Fibroblast growth factor 21 (FGF21) beneficially affects taste preferences and obesity, but its action has mainly been studied in males. The aim of this study was to compare the effects of FGF21 on food preferences and glucose and lipid metabolism in C57Bl/6J male and female mice with diet-induced obesity. Mice were injected with FGF21 or vehicle for 7 days. Body weight, choice between standard (SD) and high-fat (HFD) diets, blood parameters, and gene expression in white (WAT) and brown (BAT) adipose tissues, liver, muscles, and the hypothalamus were assessed. Compared to males, females had a greater preference for HFD; less WAT; lower levels of cholesterol, glucose, and insulin; and higher expression of Fgf21, Insr, Ppara, Pgc1, Acca and Accb in the liver and Dio2 in BAT. FGF21 administration decreased adiposity; blood levels of cholesterol, glucose, and insulin; hypothalamic Agrp expression, increased SD intake, decreased HFD intake independently of sex, and increased WAT expression of Pparg, Lpl and Lipe only in females. Thus, FGF21 administration beneficially affected mice of both sexes despite obesity-associated sex differences in metabolic characteristics, and it induced female-specific activation of gene expression in WAT. 相似文献
8.
Josca M. Schoonejans Heather L. Blackmore Thomas J. Ashmore Catherine E. Aiken Denise S. Fernandez-Twinn Susan E. Ozanne 《International journal of molecular sciences》2021,22(15)
Background: Metformin is commonly used to treat gestational diabetes mellitus. This study investigated the effect of maternal metformin intervention during obese glucose-intolerant pregnancy on the gonadal white adipose tissue (WAT) of 8-week-old male and female mouse offspring. Methods: C57BL/6J female mice were provided with a control (Con) or obesogenic diet (Ob) to induce pre-conception obesity. Half the obese dams were treated orally with 300 mg/kg/d of metformin (Ob-Met) during pregnancy. Gonadal WAT depots from 8-week-old offspring were investigated for adipocyte size, macrophage infiltration and mRNA expression of pro-inflammatory genes using RT-PCR. Results: Gestational metformin attenuated the adiposity in obese dams and increased the gestation length without correcting the offspring in utero growth restriction and catch-up growth caused by maternal obesity. Despite similar body weight, the Ob and Ob-Met offspring of both sexes showed adipocyte hypertrophy in young adulthood. Male Ob-Met offspring had increased WAT depot weight (p < 0.05), exaggerated adipocyte hyperplasia (p < 0.05 vs. Con and Ob offspring), increased macrophage infiltration measured via histology (p < 0.05) and the mRNA expression of F4/80 (p < 0.05). These changes were not observed in female Ob-Met offspring. Conclusions: Maternal metformin intervention during obese pregnancy causes excessive adiposity, adipocyte hyperplasia and WAT inflammation in male offspring, highlighting sex-specific effects of prenatal metformin exposure on offspring WAT. 相似文献
9.
Metformin Reduces Lipogenesis Markers in Obese Mice Fed a Low-Carbohydrate and High-Fat Diet
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Karla Nayara de Oliveira Santana Deborah Farias Lelis Keila Lopes Mendes Jamille Fernandes Lula Alanna Fernandes Paraíso João Marcus Oliveira Andrade John David Feltenberger Junio Cota Diego Vicente da Costa Alfredo Mauricio Batista de Paula André Luiz Sena Guimarães Sérgio Henrique Sousa Santos 《Lipids》2016,51(12):1375-1384
Lipogenesis is the process by which fatty acids are synthesized. In metabolic syndrome, an insulin resistant state along with high plasma levels of free fatty acids (FFA) and hyperglycemia may contribute to the lipogenic process. The aim of the present study was to investigate the effects of oral administration of metformin on the expression of lipogenic genes and glycemic profile in mice fed with low‐carbohydrate high‐fat diet by evaluating their metabolic profile. SWISS male mice were divided into 4 groups (N = 7) that were fed with standard (ST), standard plus metformin (ST + MET), low‐carbohydrate high‐fat diet (LCHFD) and low‐carbohydrate high‐fat diet plus metformin (LCHFD + MET) (100 mg kg?1 diet) diets respectively. Food intake, body weight and blood parameters, such as glucose tolerance, insulin sensitivity, glucose, HDL‐c, total cholesterol, triglycerides, ASL and ALT levels were assessed. Histological analyses were performed on hematoxylin and eosin‐stained epididymal adipose tissue histological specimens. The expression levels of peroxisome proliferator‐activated receptor (PPARγ), sterol regulatory element‐binding protein 1 (SREBP1), fatty acid synthase (FAS) and acetyl‐CoA carboxylase (ACC), were assessed by RT‐PCR. This study showed that metformin decreased adipocyte area, body weight and food consumption in obese animals when compared to the standard group. Furthermore, the expression of lipogenic markers in adipose tissue were diminished in obese animals treated with metformin. This data showed that oral administration of metformin improved glucose and lipid metabolic parameters in white adipose tissue by reducing the expression of lipogenesis markers, suggesting an important clinical application of MET in treating obesity‐related diseases in metabolic syndrome. 相似文献
10.
Abnormalities in the Metabolism of Fatty Acids and Triacylglycerols in the Liver of the Goto-Kakizaki Rat: A Model for Non-Obese Type 2 Diabetes
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Minako Karahashi Yuko Hirata-Hanta Kohei Kawabata Daisuke Tsutsumi Misaki Kametani Nanako Takamatsu Takeshi Sakamoto Tohru Yamazaki Satoshi Asano Atsushi Mitsumoto Yoichi Kawashima Naomi Kudo 《Lipids》2016,51(8):955-971
11.
Hsiao-Pei Tsai Po-Hsun Hou Frank-Chiahung Mao Chia-Chia Chang Wei-Cheng Yang Ching-Feng Wu Huei-Jyuan Liao Tzu-Chun Lin Lan-Szu Chou Li-Wei Hsiao Geng-Ruei Chang 《International journal of molecular sciences》2021,22(1)
Risperidone, a second-generation antipsychotic drug used for schizophrenia treatment with less-severe side effects, has recently been applied in major depressive disorder treatment. The mechanism underlying risperidone-associated metabolic disturbances and liver and renal adverse effects warrants further exploration. This research explores how risperidone influences weight, glucose homeostasis, fatty liver scores, liver damage, and renal impairment in high-fat diet (HFD)-administered C57BL6/J mice. Compared with HFD control mice, risperidone-treated obese mice exhibited increases in body, liver, kidney, and retroperitoneal and epididymal fat pad weights, daily food efficiency, serum triglyceride, blood urea nitrogen, creatinine, hepatic triglyceride, and aspartate aminotransferase, and alanine aminotransferase levels, and hepatic fatty acid regulation marker expression. They also exhibited increased insulin resistance and glucose intolerance but decreased serum insulin levels, Akt phosphorylation, and glucose transporter 4 expression. Moreover, their fatty liver score and liver damage demonstrated considerable increases, corresponding to increases in sterol regulatory element-binding protein 1 mRNA, fatty acid-binding protein 4 mRNA, and patatin-like phospholipid domain containing protein 3 expression. Finally, these mice demonstrated renal impairment, associated with decreases in glutathione peroxidase, superoxide dismutase, and catalase levels. In conclusion, long-term administration of risperidone may exacerbate diabetes syndrome, nonalcoholic fatty liver disease, and kidney injury. 相似文献
12.
Magdalena J. M. Marschall Robert Ringseis Denise K. Gessner Sarah M. Grundmann Erika Most Gaiping Wen Garima Maheshwari Holger Zorn Klaus Eder 《International journal of molecular sciences》2021,22(10)
Conflicting reports exist with regard to the effect of ecdysterone, the predominating representative of steroid hormones in insects and plants, on hepatic and plasma lipid concentrations in different rodent models of obesity, fatty liver, and diabetes, indicating that the effect is dependent on the rodent model used. Here, the hypothesis was tested for the first time that ecdysterone causes lipid-lowering effects in genetically obese Zucker rats. To test this hypothesis, two groups of male obese Zucker rats (n = 8) were fed a nutrient-adequate diet supplemented without or with 0.5 g ecdysterone per kg diet. To study further if ecdysterone is capable of alleviating the strong lipid-synthetic activity in the liver of obese Zucker rats, the study included also two groups of male lean Zucker rats (n = 8) which also received either the ecdysterone-supplemented or the non-supplemented diet. While hepatic and plasma concentrations of triglycerides and cholesterol were markedly higher in the obese compared to the lean rats (p < 0.05), hepatic and plasma triglyceride and cholesterol concentrations did not differ between rats of the same genotype fed the diets without or with ecdysterone. In conclusion, the present study clearly shows that ecdysterone supplementation does not exhibit lipid-lowering actions in the liver and plasma of lean and obese Zucker rats. 相似文献
13.
14.
Rice Bran Oil Improves Insulin Resistance by Affecting the Expression of Antioxidants and Lipid‐Regulatory Genes
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Mervat A. Ahmed Mona A. Mohamed Laila A. Rashed Sohaier A. Abd Elbast Elham A. Ahmed 《Lipids》2018,53(5):505-515
The present study investigated the molecular effects of rice bran oil (RBO) on lipid‐regulatory genes (sterol regulatory element binding protein‐1 [Srebf1] and peroxisome proliferator‐activated receptors‐α [Ppara]) and the expression of catalase (CAT) and superoxide dismutase (SOD1) genes in insulin‐resistant rats. Rats were divided into five groups: animals that received standard diet (control); rats fed standard diet containing RBO as the sole source of fat (RBO); a high‐fructose diet (HFD) group, which was further divided into two subgroups: rats fed HFD either for only 1 month (HFD1) or for 2 months (HFD2) and rats fed HFD containing RBO for 1 month; while rats in the last group fed HFD for 30 days then treated with RBO for another 30 days. The HFD induced a state of insulin resistance (IR) as indicated by the hyperinsulinemia and elevated homeostasis model assessment insulin resistance index. Hepatic lipid levels and radical scavenging enzymes were altered by the HFD. Lipid‐regulatory genes, Srebf1 and Ppara, were upregulated while Sod1 and Cat were downregulated in insulin‐resistant rats. Addition of RBO to the two diet regimens alleviated the disorders of IR to some extent. RBO reduced the hepatic levels of triacylglycerol, malondialdehyde, SREBP, and PPAR‐α mRNA. Hepatic SOD and CAT were elevated at gene and protein levels. The HFD induces de novo lipogenesis by upregulating the lipid‐regulatory genes resulting in increased serum and hepatic triacylglycerol. Moreover, IR induced by the HFD caused a state of oxidative stress. Supplementation of RBO to fructose‐fed rats not only improves insulin resistance but also downregulates lipogenic genes and improves the unbalanced oxidative status. 相似文献
15.
Cutaneous fatty acid-binding protein (C-FABP) is a member of the intracellular lipid-binding protein multigene family expressed in various tissues. A high level of C-FABP mRNA in adipose tissue has been reported, but its physiological significance in regulating adipose tissue function is not clear. To obtain insights into the role of C-FABP in adipose tissue, we studied the obesity-related and dietary fat-related changes of C-FABP mRNA expression in adipose tissues. C-FABP mRNA levels in interscapular brown adipose tissue, and epididymal and perirenal white adipose tissues were higher in Zucker fatty rats than in lean controls despite that the difference in brown adipose tissue was not significant. Fish oil compared to palm and safflower oils significantly reduced the mRNA level of C-FABP in brown adipose tissue and epididymal and perirenal white adipose tissues in Sprague-Dawley rats except for one occasion. Our study demonstrated that C-FABP is a protein whose mRNA expression is easily modified by hereditary obesity and the type of dietary fat. Therefore, C-FABP may play a significant role in regulating adipocyte function in response to changes in nutritional conditions. 相似文献
16.
High-Fat Diet Alters Serum Fatty Acid Profiles in Obesity Prone Rats: Implications for In Vitro Studies
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Liu Tzu-Wen Heden Timothy D. Matthew Morris E. Fritsche Kevin L. Vieira-Potter Victoria J. Thyfault John P. 《Lipids》2015,50(10):997-1008
High‐fat diets (HFD) are commonly used in rodents to induce obesity, increase serum fatty acids and induce lipotoxicity in various organs. Invitro studies commonly utilize individual free fatty acids (FFA) to study lipid exposure in an effort to model what is occurring in vivo; however, these approaches are not physiological as tissues are exposed to multiple fatty acids in vivo. Here we characterize circulating lipids in obesity‐prone rats fed an HFD in both fasted and fed states with the goal of developing physiologically relevant fatty acid mixtures for subsequent in vitro studies. Rats were fed an HFD (60 % kcal fat) or a control diet (10 % kcal fat) for 3 weeks; liver tissue and both portal and systemic blood were collected. Fatty acid profiles and absolute concentrations of triglycerides (TAG) and FFA in the serum and TAG, diacylglycerol (DAG) and phospholipids in the liver were measured. Surprisingly, both systemic and portal serum TAG were ~40 % lower in HFD‐fed compared to controls. Overall, compared to the control diet, HFD feeding consistently induced an increase in the proportion of circulating polyunsaturated fatty acids (PUFA) with a concomitant decline in monounsaturated fatty acids (MUFA) and saturated fatty acids (SFA) in both serum TAG and FFA. The elevations of PUFA were mostly attributed to increases in n‐6 PUFA, linoleic acid and arachidonic acid. In conclusion, fatty acid mixtures enriched with linoleic and arachidonic acid in addition to SFA and MUFA should be utilized for in vitro studies attempting to model lipid exposures that occur during in vivo HFD conditions. 相似文献
17.
High free fatty acid (FFA) levels are common in obesity and in diseases such as diabetes that are associated with the obese
state. Dehydroepiandrosterone (DHEA) decreases dietary fat consumption, body fat content, and insulin levels in the obese
Zucker rat (ZR), a genetic model of human youth-onset obesity and type 2 diabetes mellitus. This study was conducted to investigate
the effects of DHEA on lean and obese ZR serum, adipose, and hepatic tissue fatty acid (FA) profiles and serum FFA levels.
Because DHEA is known to decrease fat consumption and body fat, we postulate that DHEA may also alter FA profiles and FFA
levels of the obese ZR such that they more closely resemble the profiles and levels of their lean siblings. In this study
there was a DHEA and a pair-fed (PF) group (n=6) for 12 lean and 12 obese ZR. The diet of the treatment groups was supplemented with 0.6% DHEA, and PF groups were given
the same average calories consumed by their corresponding DHEA group for 30 d. Fasted animals were sacrificed, and FA profiles
and FFA levels were measured. Serum FFA levels were higher in obese (∼1 mmol/L) compared to lean rats (∼0.6 mmol/L). After
30 d of DHEA treatment, FFA levels were lower (P<0.05) in both lean and obese groups. Although several significant differences in FA profile of serum, hepatic, and adipose
lipid components were observed between lean and obese ZR, DHEA-related changes were only observed in the serum phospholipid
(PL) and liver PL and triglyceride fractions. The slight but significant decrease in serum FFA levels may be reflected by
changes in serum PL FA profiles. Specific hepatic FA profile alterations may be related to DHEA's known effects in inducing
hepatic peroxisomes. We speculate that such FA changes may give insight into a mechanism for the action of DHEA. 相似文献
18.
An Ester of β-Hydroxybutyrate Regulates Cholesterol Biosynthesis in Rats and a Cholesterol Biomarker in Humans
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Martin F. Kemper Shireesh Srivastava M. Todd King Kieran Clarke Richard L. Veech Robert J. Pawlosky 《Lipids》2015,50(12):1185-1193
In response to carbohydrate deprivation or prolonged fasting the ketone bodies, β‐hydroxybutyrate (βHB) and acetoacetate (AcAc), are produced from the incomplete β‐oxidation of fatty acids in the liver. Neither βHB nor AcAc are well utilized for synthesis of sterols or fatty acids in human or rat liver. To study the effects of ketones on cholesterol homeostasis a novel βHB ester (KE) ((R)‐3‐hydroxybutyl (R)‐3‐hydroxybutyrate) was synthesized and given orally to rats and humans as a partial dietary carbohydrate replacement. Rats maintained on a diet containing 30‐energy % as KE with a concomitant reduction in carbohydrate had lower plasma cholesterol and mevalonate (?40 and ?27 %, respectively) and in the liver had lower levels of the mevalonate precursors acetoacetyl‐CoA and HMG‐CoA (?33 and ?54 %) compared to controls. Whole liver and membrane LDL‐R as well as SREBP‐2 protein levels were higher (+24, +67, and +91 %, respectively). When formulated into a beverage for human consumption subjects consuming a KE drink (30‐energy %) had elevated plasma βHB which correlated with decreased mevalonate, a liver cholesterol synthesis biomarker. Partial replacement of dietary carbohydrate with KE induced ketosis and altered cholesterol homeostasis in rats. In healthy individuals an elevated plasma βHB correlated with lower plasma mevalonate. 相似文献
19.
Yujin Shin Mijeong Lee Dongju Lee Joonseong Jang Soon Shik Shin Michung Yoon 《International journal of molecular sciences》2021,22(7)
Fibrates, including fenofibrate, are a class of hypolipidemic drugs that activate peroxisome proliferator-activated receptor α (PPARα), which in-turn regulates the expression of lipid and lipoprotein metabolism genes. We investigated whether fenofibrate can reduce visceral obesity and nonalcoholic fatty liver disease via adipose tissue PPARα activation in female ovariectomized (OVX) C57BL/6J mice fed a high-fat diet (HFD), a mouse model of obese postmenopausal women. Fenofibrate reduced body weight gain (−38%, p < 0.05), visceral adipose tissue mass (−46%, p < 0.05), and visceral adipocyte size (−20%, p < 0.05) in HFD-fed obese OVX mice. In addition, plasma levels of alanine aminotransferase and aspartate aminotransferase, as well as free fatty acids, triglycerides, and total cholesterol, were decreased. Fenofibrate also inhibited hepatic lipid accumulation (−69%, p < 0.05) and infiltration of macrophages (−72%, p < 0.05), while concomitantly upregulating the expression of fatty acid β-oxidation genes targeted by PPARα and decreasing macrophage infiltration and mRNA expression of inflammatory factors in visceral adipose tissue. These results suggest that fenofibrate inhibits visceral obesity, as well as hepatic steatosis and inflammation, in part through visceral adipose tissue PPARα activation in obese female OVX mice. 相似文献
20.
Lutein Prevents High Fat Diet‐Induced Atherosclerosis in ApoE‐Deficient Mice by Inhibiting NADPH Oxidase and Increasing PPAR Expression
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Hao Han Wei Cui Linzhi Wang Yufang Xiong Liegang Liu Xiufa Sun Liping Hao 《Lipids》2015,50(3):261-273
Epidemiological and experimental studies provide supportive evidence that lutein, a major carotenoid, may act as a chemopreventive agent against atherosclerosis, although the underlying molecular mechanisms are not well understood. The main aim of this study was to investigate the effects of lutein on the alleviation of atherosclerosis and its molecular mechanisms involved in oxidative stress and lipid metabolism. Male apolipoprotein E knockout mice (n = 55) were fed either a normal chow diet or a high fat diet (HFD) supplemented with or without lutein for 24 weeks. The results showed that a HFD induced atherosclerosis formation, lipid metabolism disorders and oxidative stress, but noticeable improvements were observed in the lutein treated group. Additionally, lutein supplementation reversed the decreased protein expression of aortic heme oxygenase‐1 and increased the mRNA and protein expressions of aortic nicotinamide‐adenine dinucleotide phosphate oxidase stimulated by a HFD. Furthermore, the decreased mRNA and protein expression levels of hepatic peroxisome proliferator‐activated receptor‐α, carnitine palmitoyltransferase 1A, acyl CoA oxidase 1, low density lipoprotein receptors and scavenger receptor class B type I observed in mice with atherosclerosis were markedly enhanced after treatment with lutein. Taken together, these data add new evidence supporting the anti‐atherogenic properties of lutein and describing its mechanisms of action in atherosclerosis prevention, including oxidative stress and lipid metabolism improvements. 相似文献