Abstract 456: Comparative Effects of Angiotensinogen versus Renin Inhibition on Established Atherosclerosis and Obesity in Hypercholesterolemic Mice

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Anju Balakrishnan ◽  
Deborah A Howatt ◽  
Hong Lu ◽  
Mark J Graham ◽  
Adam E Mullick ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Critical Role ◽  
Ldl Receptor ◽  
Saturated Fat ◽  
Renin Angiotensin System ◽  
Reduced Body ◽  
Renin Inhibition

Background and Objective The renin angiotensin system plays a critical role in atherosclerosis. Inhibition of angiotensinogen (AGT) or renin prevents atherosclerosis. AGT inhibition also ablates diet induced obesity. The purpose of this study was to compare the effects of AGT and renin inhibition on established atherosclerosis and obesity. Methods and Results To determine the role of AGT, male LDL receptor -/- mice were fed a saturated fat-enriched diet for 12 weeks to establish atherosclerosis (N=80). Body weight increased about 1 g/week in the 12-week duration. Twenty mice were then terminated to assess baseline atherosclerosis, and the remaining mice were randomly grouped to administer either control- or AGT-antisense oligonucleotides (ASO) (50 mg/kg/week ip; N=20/group) for 12 weeks. To determine the role of renin inhibition, male LDL receptor -/- mice were fed the same fat-enriched diet for 16 weeks (N=55). Mean body weight gain was about 1 g/week. Twenty-one mice were terminated to assess baseline atherosclerosis, and the remaining mice were randomly grouped to infuse either PBS (N=24) or aliskiren (12.5 mg/kg/d; N=10) for 12 weeks. Inhibition of AGT or renin significantly decreased systolic blood pressure. Atherosclerotic lesions were quantified in the aortic arch. Inhibition of either AGT or renin attenuated the rogression of atherosclerosis as compared to their relative controls (P=0.047 and P≤0.001, respectively), whereas neither mode of inhibition regressed atherosclerosis compared to their respective baseline. Renin inhibition did not influence the fat diet-induced body weight gain. Surprisingly, inhibition of AGT not only abolished body weight gain, but also led to pronounced loss of body weight (baseline versus 12-week injection of AGT-ASO: 36.0±0.8 versus 32.2±0.9 g; P<0.001). Echo MRI analyses demonstrated that the lower body weight in mice administered AGT-ASO was attributed to less fat mass, while lean mass was comparable between control-ASO and AGT-ASO groups. Conclusions Inhibition of either AGT or renin attenuated the continued development of atherosclerosis. Inhibition of AGT also profoundly reduced body weight. This highlights a disparity between the two modes of RAS inhibition.

Abstract 444: Angiotensinogen Inhibition Reduces Atherosclerosis and Body Weight Gain Induced by High-Carbohydrate Diet

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Anju Balakrishnan ◽  
Deborah A Howatt ◽  
Congqing Wu ◽  
Adam E Mullick ◽  
Mark J Graham ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Plasma Cholesterol ◽  
Ldl Receptor ◽  
Renin Angiotensin System ◽  
High Carbohydrate Diet ◽  
Carbohydrate Diet ◽  
High Carbohydrate ◽  
Aortic Arches

Background and Objective: Angiotensinogen (AGT) is the unique precursor of the renin angiotensin system. Our previous studies demonstrated that inhibition of AGT markedly reduced development of atherosclerosis and ablated body weight gain induced by a saturated fat-enriched diet. In addition to high fat intake, high carbohydrate consumption is an important component of contemporary diets. The purpose of this study was to determine whether AGT inhibition prevented atherosclerosis and obesity in LDL receptor -/- mice fed a high carbohydrate diet. Methods and Results: Eight week old male LDL receptor -/- mice were randomized to receive either control or AGT antisense oligonucleotides (ASO; 50 mg/kg/week intraperitoneal injection; N = 10 mice/group). Feeding a high carbohydrate diet was initiated after 6 weeks of ASO injection, and maintained for 12 weeks with continuous ASO injection. AGT-ASO administration profoundly reduced plasma AGT concentrations (Control vs AGT ASO: 3582 ± 117 vs 227 ± 15 ng/ml; P<0.001). High carbohydrate diet feeding resulted in profound increases of plasma cholesterol concentrations in both groups. Atherosclerotic lesions in aortic arches were measured using an en face method after termination. AGT inhibition led to significant decreases (P<0.001) in percentage lesion areas of aortic arches. Prior to high carbohydrate diet feeding, there was no difference of body weight between the two groups (Control vs AGT ASO: 26.6 ± 0.6 vs 25.9 ± 0.7 g; P=0.4). Although high carbohydrate diet only increased body weight modestly, mice injected with AGT ASO had less increases of body weight compared to mice injected with control ASO (Control vs AGT ASO: 28.5 ± 0.6 vs 26.8 ± 0.6 g; P<0.05). Echo MRI analyses demonstrated that the lower body weight in mice administered AGT ASO was attributed to less fat mass gain, whereas lean mass was comparable between the two groups. Additionally, AGT inhibition resulted in lower blood hemoglobin A1c (5.5 ± 0.1 vs 5.1 ± 0.1%; P=0.005). Conclusions: AGT inhibition reduces high carbohydrate diet-induced atherosclerosis and body weight gain.

scholarly journals Effect of Heat Stress on Body Weight Gain, Heterophile-Lymphocite Ratio and Body Temperature in Broiler

2016 ◽  
Vol 3 (1) ◽  
Author(s):  
Sugito S ◽  
Mira Delima
Keyword(s):  
Body Weight ◽  
Heat Stress ◽  
Weight Gain ◽  
Body Temperature ◽  
Broiler Chicken ◽  
Body Weight Gain ◽  
Conversion Ratio ◽  
Feed Conversion Ratio ◽  
Feed Conversion ◽  
Reduced Body

Increasing in ambient temperature inside the cage could lead to heat stress in broilers. This research was conducted to find out effects of heat stress on body weight gain, heterophile-lymphocite ratio and body temperature in chicken broiler. Twenty broilers aged 20 days (strain Cobb) were randomly divided into 2 groups. The first group was treated with no heat stress, the second one was caged in 33±1 0C temperature for 4 hours per day for 14 days. The results indicated that heat stress reduced body weight gain, increased body temperature, and changed behavior, but no effect on feed conversion ratio (FCR) and heterophile-lymphocyte ratio. It suggested that the heat stress caused detrimental effects on broiler chicken.

scholarly journals Cigarette smoking blocks the benefit from reduced weight gain for insulin action by shifting lipids deposition to muscle

2020 ◽  
Vol 134 (13) ◽  
pp. 1659-1673
Author(s):  
Anwar Khan ◽  
Sherouk Fouda ◽  
Ali Mahzari ◽  
Stanley M.H. Chan ◽  
Xiu Zhou ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Cigarette Smoking ◽  
Mrna Expression ◽  
Glucose Intolerance ◽  
Insulin Action ◽  
Insulin Signalling ◽  
Body Weight Gain ◽  
Hormone Sensitive Lipase ◽  
Reduced Body

Abstract Cigarette smoking (CS) is known to reduce body weight and this often masks its real effect on insulin action. The present study tested the hypothesis that CS can divert lipid deposition to muscles to offset the supposed benefit of reduced body weight gain on insulin signalling in this major site for glucose tolerance (or insulin action). The study was conducted in mice exposed to chronic CS followed by either a chow (CH) diet or a high-fat (HF) diet. CS increased triglyceride (TG) levels in both plasma and muscle despite a reduced body weight gain and adiposity. CS led to glucose intolerance in CH-fed mice and they retained the glucose intolerance that was induced by the HF diet. In adipose tissue, CS increased macrophage infiltration and the mRNA expression of TNFα but suppressed the protein expression of adipose triglyceride lipase and PPARγ. While CS increased hormone-sensitive lipase and suppressed the mRNA expression of leptin, these effects were blunted in HF-fed mice. These results imply that CS impairs insulin signalling in skeletal muscle via accumulated intramuscular lipids from lipolysis and lipodystrophy of adipose tissues. This may explain why smokers may not benefit from insulin sensitising effects of reduced body weight gain.

scholarly journals Effects of estradiol and progesterone on food intake, body weight, and carcass adiposity in weanling rats

1981 ◽  
Vol 240 (5) ◽  
pp. E499-E503 ◽  
Author(s):  
S. M. Schwartz ◽  
G. N. Wade
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Estradiol Benzoate ◽  
Female Rats ◽  
Reduce Food Intake ◽  
Reduced Body ◽  
Adipose Tissue Lipoprotein Lipase

The effects of estradiol and progesterone on food intake, body weight, carcass adiposity, and adipose tissue lipoprotein lipase (LPL) activity were investigated in weanling female rats. Treatment with estradiol benzoate (EB) reduced body weight gain in ovariectomized (OVX) weanlings as it does in adults. However, other responses to EB were attenuated or absent in weanlings. EB treatment did not reduce food intake, carcass adiposity, or adipose tissue LPL activity. This impaired responsiveness to EB may be due to decreased levels of cytoplasmic estrogen receptors in liver and adipose tissue (but not hypothalamus) in weanlings. On the other hand, responsiveness to progesterone was adultlike in weanlings. Treatment of OVX, EB-primed weanlings with progesterone increased food intake, body weight gain, and carcass adiposity. This adultlike responsiveness to progesterone was associated with adultlike levels of adipose tissue progestin receptors. However, progesterone treatment did not increase adipose tissue LPL activity in weanlings, indicating that changes in LPL activity are not necessary for progesterone-induced obesity.

scholarly journals Adipose tissue transplantation protects ob/ob mice from obesity, normalizes insulin sensitivity and restores fertility

2005 ◽  
Vol 186 (1) ◽  
pp. 203-211 ◽  
Author(s):  
Simon Klebanov ◽  
Clinton M Astle ◽  
Olga DeSimone ◽  
Vitaly Ablamunits ◽  
David E Harrison
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Therapeutic Potential ◽  
Body Weight Gain ◽  
Hormone Replacement ◽  
Tolerance Test ◽  
Reduced Body ◽  
Insulin Tolerance

Adipose tissue affects metabolism by secreting various adipokines. Lipodystropic mice benefit both from leptin replacement therapy and from transplantation of normal fat. Leptin-deficient Lepob/Lepob (ob/ob) mice can also be treated with leptin. Surprisingly, there have been no reports of successful treatment of obese ob/ob mice by transplantation of normal white adipose tissue (WAT). If WAT transplantation is ineffective in treating insulin resistance and diabetes in obese individuals, its applicability may be limited in humans as such abnormalities are usually associated with obesity. In the current study, we tested whether WAT transplantation might prevent, and even reverse, abnormalities characteristic of ob/ob mice. To assess the preventive potential, 6-week-old ob/ob mice were transplanted, subcutaneously, with gonadal fat pads from normal mice. Profound effects on multiple physiological phenotypes were achieved despite leptin levels below 25% of those in control mice. WAT from one donor reduced body weight gain, and WAT from 4 or 8 donors prevented obesity in ob/ob mice. Nonfasting insulin levels and insulin tolerance test were normalized. Corticosterone elevation was also prevented. Finally, WAT from 4 donors restored fertility in ob/ob females. The effects of WAT transplantation were long-lasting, with body weight gain suppressed for at least 40 weeks. To assess the therapeutic potential, obese 13-month-old ob/ob mice with a long history of leptin deficiency were used. Their body weight decreased by approximately 50% when transplanted with WAT from 8 donors. As in young recipients, transplantation greatly reduced nonfasting insulin, suggesting normalized insulin sensitivity. Thus, WAT transplantation was effective for both prevention and therapy. In the future, WAT transplantation may become a useful alternative to hormone replacement in treating not only lipodystropy, but also certain types of obesity.

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