scholarly journals Distinct Effects of a High Fat Diet on Bone in Skeletally Mature and Developing Male C57BL/6J Mice

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1666
Author(s):  
Dean S. Ross ◽  
Tzu-Hsuan Yeh ◽  
Shalinie King ◽  
Julia Mathers ◽  
Mark S. Rybchyn ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Bone Formation ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
Age Groups ◽  
Oral Glucose ◽  
Rna Expression ◽  
High Fat ◽  
Mineral Density ◽  
Skeletal Fragility

Increased risks of skeletal fractures are common in patients with impaired glucose handling and type 2 diabetes mellitus (T2DM). The pathogenesis of skeletal fragility in these patients remains ill-defined as patients present with normal to high bone mineral density. With increasing cases of glucose intolerance and T2DM it is imperative that we develop an accurate rodent model for further investigation. We hypothesized that a high fat diet (60%) administered to developing male C57BL/6J mice that had not reached skeletal maturity would over represent bone microarchitectural implications, and that skeletally mature mice would better represent adult-onset glucose intolerance and the pre-diabetes phenotype. Two groups of developing (8 week) and mature (12 week) male C57BL/6J mice were placed onto either a normal chow (NC) or high fat diet (HFD) for 10 weeks. Oral glucose tolerance tests were performed throughout the study period. Long bones were excised and analysed for ex vivo biomechanical testing, micro-computed tomography, 2D histomorphometry and gene/protein expression analyses. The HFD increased fasting blood glucose and significantly reduced glucose tolerance in both age groups by week 7 of the diets. The HFD reduced biomechanical strength, both cortical and trabecular indices in the developing mice, but only affected cortical outcomes in the mature mice. Similar results were reflected in the 2D histomorphometry. Tibial gene expression revealed decreased bone formation in the HFD mice of both age groups, i.e., decreased osteocalcin expression and increased sclerostin RNA expression. In the mature mice only, while the HFD led to a non-significant reduction in runt-related transcription factor 2 (Runx2) RNA expression, this decrease became significant at the protein level in the femora. Our mature HFD mouse model more accurately represents late-onset impaired glucose tolerance/pre-T2DM cases in humans and can be used to uncover potential insights into reduced bone formation as a mechanism of skeletal fragility in these patients.

Abstract 19498: Scavenger Receptor BI (SR-BI) Deficiency Uncouples Obesity From Glucose Intolerance in Mice

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Menno Hoekstra ◽  
Amber B Ouweneel ◽  
Miranda Van Eck
Keyword(s):  
Body Weight ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
Cholesterol Metabolism ◽  
Scavenger Receptor ◽  
Oral Glucose ◽  
High Fat ◽  
Scavenger Receptor Bi ◽  
Obesity In Mice

Introduction: Scavenger receptor BI (SR-BI) is a multi-purpose player in cholesterol metabolism. Interestingly, several studies in humans have suggested that a significant relationship exists between the presence of common variants in the SR-BI gene and a higher body mass index. We therefore evaluated the contribution of SR-BI to high fat diet-induced obesity in mice. Methods and Results: Male SR-BI knockout (SR-BI KO; N=10) and wild-type (WT; N=9) mice were fed a diet containing 45% energy as fat for 12 weeks. SR-BI KO mice exhibited a worsened metabolic plasma profile as compared to WT controls with higher fasting levels of free cholesterol (+111%; P<0.001), cholesterol esters (+84%; P<0.001), triglycerides (+40%; P<0.01), and glucose (+20%; P<0.01). Daily food intake was similar in the two types of mice; 4.5±0.3 g for SR-BI KO vs 4.1±0.3 g for WT. Importantly, the relative increase in body weight over time was significantly greater in SR-BI KO mice (+51%) as compared to WT controls (+33%; two-way ANOVA P<0.001 for genotype). The exacerbated increase in body weight could be attributed to a higher white adipose tissue mass (correlation coefficient R=0.87; P<0.001). High fat diet-fed WT mice were glucose intolerant, but remained resistant to atherosclerosis. In contrast, atherosclerotic lesions could be readily detected in the aortic root of SR-BI KO mice (6.9±1.5 x 10 3 μm 2 ; P<0.001), while their glucose tolerance was remarkably higher compared to that of controls (oral glucose tolerance test AUC 484±68 mM.min for SR-BI KO vs 875±130 mM.min for WT; P<0.05). SR-BI deficiency thus uncouples obesity from glucose intolerance in mice. Conclusions: Our studies for the first time show that a proper SR-BI function inhibits the development of obesity in mice. Furthermore, these data imply that SR-BI may serve as therapeutic target to overcome the glucose intolerance normally associated with the presence of (morbid) obesity.

scholarly journals Patchouli Alcohol from Pogostemon Cablin Prevents Development of Obesity and Improves Glucose Tolerance in High Fat Diet-induced Obese Mice (P06-107-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jihye Lee ◽  
Seong-Ho Lee
Keyword(s):  
Body Weight ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Oral Glucose ◽  
Male Mice ◽  
Fat Pad ◽  
High Fat ◽  
Patchouli Alcohol ◽  
Brown Adipose ◽  
Pogostemon Cablin

Abstract Objectives Patchouli alcohol is a sesquiterpene alcohol found in Pogostemon cablin. Recently, we observed that patchouli alcohol reduced lipid accumulation in differentiated 3T3-L1 adipocytes and increased glucose uptake in differentiated C2C12 myocytes. This study was designed to investigate anti-obese and anti-diabetic activities of patchouli alcohol using high fat diet-induced obese mouse model. Methods Forty-eight 5-week old C57BL/6 J male mice were assigned into four groups and fed with 1) normal diet (control), 2) high fat diet, 3) high fat diet with gavaging 25 mg of patchouli alcohol/kg body weight and 4) high fat diet with gavaging 50 mg of patchouli alcohol/kg body weight. High fat diet or control diets were provided to each treatment group for four weeks and then different doses of patchouli alcohol (0, 25 or 50 mg/kg body weight) was orally administered for following 8 weeks with the diet. At age of week 17, all animals were sacrificed, fat tissues were collected, and tissue weight was measured. In addition, twenty C57BL/6 J male mice were assigned into the same treatment groups above. At the end of the 8 weeks (age of week 17), the mice were fasted for 12 h and the oral glucose tolerance test was performed after intraperitoneal injection of 2 g of anhydrous glucose/kg body weight. The blood was collected from tail at 0, 15, 30, 90 and 120 min after injection and blood glucose level was analyzed using glucose meter. Results Treatment of patchouli alcohol (50 mg/kg body weight) significantly reduced body weight and accumulation of body fat pads which was highly induced by feeding of high fat diet. An analysis of individual fat pad weights (expressed as mg weight of fat pad/g body weight) revealed a significant decrease of epididymal and retroperitoneal fat pad in patchouli alcohol-treated mice whereas brown adipose tissue were not significantly altered. And, slightly improved glucose tolerance was observed at 90 and 120 minutes after glucose injection in mice treated with patchouli alcohol (50 mg/kg body weight) compared to those fed with high fat diet alone. Conclusions We propose a potential use of patchouli alcohol as an anti-obesity compound in obese population. Funding Sources NIFA Hatch grant. Supporting Tables, Images and/or Graphs

scholarly journals Effect of stevia on the gut microbiota and glucose tolerance in a murine model of diet-induced obesity

2020 ◽  
Vol 96 (6) ◽  
Author(s):  
Sarah L Becker ◽  
Edna Chiang ◽  
Anna Plantinga ◽  
Hannah V Carey ◽  
Garret Suen ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Gut Microbiota ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
High Fat ◽  
Low Fat ◽  
Treatment Groups ◽  
Low Fat Diet ◽  
Taxonomic Groups ◽  
Induced Changes

ABSTRACT Artificial sweeteners have been shown to induce glucose intolerance by altering the gut microbiota; however, little is known about the effect of stevia. Here, we investigate whether stevia supplementation induces glucose intolerance by altering the gut microbiota in mice, hypothesizing that stevia would correct high fat diet-induced glucose intolerance and alter the gut microbiota. Mice were split into four treatment groups: low fat, high fat, high fat + saccharin and high fat + stevia. After 10 weeks of treatment, mice consuming a high fat diet (60% kcal from fat) developed glucose intolerance and gained more weight than mice consuming a low fat diet. Stevia supplementation did not impact body weight or glucose intolerance. Differences in species richness and relative abundances of several phyla were observed in low fat groups compared to high fat, stevia and saccharin. We identified two operational taxonomic groups that contributed to differences in beta-diversity between the stevia and saccharin groups: Lactococcus and Akkermansia in females and Lactococcus in males. Our results demonstrate that stevia does not rescue high fat diet-induced changes in glucose tolerance or the microbiota, and that stevia results in similar alterations to the gut microbiota as saccharin when administered in concordance with a high fat diet.

Effects of a Seven Day High-Fat Diet on Oral Glucose Tolerance and Endothelial Function in Young Males

2015 ◽  
Vol 47 ◽  
pp. 289-290
Author(s):  
Cody G. Durrer ◽  
Zhongxiao Wan ◽  
Nia Lewis ◽  
Philip N. Ainslie ◽  
Nathan T. Jenkins ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Endothelial Function ◽  
High Fat Diet ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
High Fat ◽  
Young Males

scholarly journals Modifications of gastric inhibitory polypeptide (GIP) secretion in man by a high-fat diet

1988 ◽  
Vol 59 (3) ◽  
pp. 373-380 ◽  
Author(s):  
L. M. Morgan ◽  
S. M. Hampton ◽  
J. A. Tredger ◽  
R. Cramb ◽  
V. Marks
Keyword(s):  
Glucose Tolerance ◽  
Energy Intake ◽  
Plasma Glucose ◽  
High Fat Diet ◽  
Gastric Inhibitory Polypeptide ◽  
Oral Glucose ◽  
Fat Intake ◽  
High Fat ◽  
C Peptide ◽  
Glucose Levels

1. Five healthy volunteers (usual fat intake 103) (SE 9) g/d and energy intake 9855 (SE 937) kJ/d were given on two separate occasions (a) 100 g oral glucose and (b) sufficient intravenous (IV) glucose to obtain similar arterialized plasma glucose levels to those after oral glucose.2. Subjects increased their fat intake by 68 (SE 9·6) % for 28 d by supplementing their diet with 146 ml double cream/d (fat intake on high-fat diet (HFD) 170 (SE 8) g/d; energy intake 12347 (SE 770)).3. The 100 g oral glucose load was repeated and IV glucose again given in quantities sufficient to obtain similar arterialized blood glucose levels. Immunoreactive plasma insulin, C-peptide and gastric inhibitory polypeptide (GIP) were measured.4. Plasma GIP levels were higher following oral glucose after the HFD (area under plasma GIP curve 0–180 min 1660 (SE 592) v. 2642 (SE 750) ng/l.h for control and HFD respectively; P < 0·05). Both insulin and C-peptide levels were significantly higher after oral than after IV glucose (P < 0·01) but neither were affected by the HFD. Glucose levels were lower following the HFD after both oral and IV glucose (area under plasma glucose curve 0–180 min, following oral glucose 6·7 (SE 0·3) mmol/l.h for control and 4·2 (SE 0·6) mmol/l.h for HFD; P < 0·01).5. Glucose-stimulated GIP secretion was thus enhanced by the HFD. Insulin secretion in response to oral glucose was unchanged, in spite of an improvement in glucose tolerance.6. The improvement in glucose tolerance post-HFD could possibly be due to a GIP-mediated inhibition of hepatic glycogenolysis, or a decreased rate of glucose uptake from the small intestine.

Fish oil ameliorates trimethylamine N-oxide-exacerbated glucose intolerance in high-fat diet-fed mice

2015 ◽  
Vol 6 (4) ◽  
pp. 1117-1125 ◽  
Author(s):  
Xiang Gao ◽  
Jie Xu ◽  
Chengzi Jiang ◽  
Yi Zhang ◽  
Yong Xue ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Fish Oil ◽  
Impaired Glucose Tolerance ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
High Fat ◽  
Dietary Fish

Dietary fish oil could ameliorate trimethylamineN-oxide (TMAO)-induced impaired glucose tolerance in HFD-fed mice.

scholarly journals Magnesium Picolinate Improves Bone Formation by Regulation of RANK/RANKL/OPG and BMP-2/Runx2 Signaling Pathways in High-Fat Fed Rats

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3353
Author(s):  
Emre Sahin ◽  
Cemal Orhan ◽  
Tansel Ansal Balci ◽  
Fusun Erten ◽  
Kazim Sahin
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
High Fat Diet ◽  
Male Rats ◽  
High Fat ◽  
Mineral Density ◽  
Protein Levels ◽  
Prevent Bone Loss ◽  
Osteogenic Protein ◽  
Affect Bone Metabolism

Magnesium (Mg) deficiency may affect bone metabolism by increasing osteoclasts, decreasing osteoblasts, promoting inflammation/oxidative stress, and result in subsequent bone loss. The objective of the present study was to identify the molecular mechanism underlying the bone protective effect of different forms of Mg (inorganic magnesium oxide (MgO) versus organic magnesium picolinate (MgPic) compound) in rats fed with a high-fat diet (HFD). Forty-two Wistar albino male rats were divided into six group (n = 7): (i) control, (ii) MgO, (iii) MgPic, (iv) HFD, (v) HFD + MgO, and (vi) HFD + MgPic. Bone mineral density (BMD) increased in the Mg supplemented groups, especially MgPic, as compared with the HFD group (p < 0.001). As compared with the HFD + MgO group, the HFD + MgPic group had higher bone P (p < 0.05) and Mg levels (p < 0.001). In addition, as compared to MgO, MgPic improved bone formation by increasing the levels of osteogenetic proteins (COL1A1 (p < 0.001), BMP2 (p < 0.001), Runx2 (p < 0.001), OPG (p < 0.05), and OCN (p < 0.001), IGF-1 (p < 0.001)), while prevented bone resorption by reducing the levels of RANK and RANKL (p < 0.001). In conclusion, the present data showed that the MgPic could increase osteogenic protein levels in bone more effectively than MgO, prevent bone loss, and contribute to bone formation in HFD rats.

scholarly journals β-cell knockout of SENP1 reduces responses to incretins and worsens oral glucose tolerance in high fat diet-fed mice

2021 ◽  
Author(s):  
Haopeng Lin ◽  
Nancy Smith ◽  
Aliya F Spigelman ◽  
Kunimasa Suzuki ◽  
Mourad Ferdaoussi ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Glucagon Secretion ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
High Fat ◽  
Β Cell ◽  
Islet Mass

SUMOylation reduces oxidative stress and preserves islet mass at the expense of robust insulin secretion. To investigate a role for the deSUMOylating enzyme <u>sen</u>trin-specific <u>p</u>rotease <u>1</u> (SENP1) following metabolic stress, we put pancreas/gut-specific SENP1 knockout mice (pSENP1-KO) on a high fat diet (HFD). Male pSENP1-KO mice were more glucose intolerant following HFD than littermate controls, but only in response to oral glucose. A similar phenotype was observed in females. Plasma glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like-peptide 1 (GLP-1) responses were identical in pSENP1-KO and -WT littermates, including the HFD-induced upregulation of GIP responses. Islet mass was not different, but insulin secretion and β-cell exocytotic responses to the GLP-1 receptor agonist Exendin-4 (Ex4) and GIP were impaired in islets lacking SENP1. Glucagon secretion from pSENP1-KO islets was also reduced, so we generated β-cell-specific SENP1 knockout mice (βSENP1-KO). These phenocopied the pSENP1-KO mice with selective impairment in oral glucose tolerance following HFD, preserved islet mass expansion, and impaired β-cell exocytosis and insulin secretion to Ex4 and GIP without changes in cAMP or Ca<sup>2+</sup> levels. Thus, β-cell SENP1 limits oral glucose intolerance following HFD by ensuring robust insulin secretion at a point downstream of incretin signaling.

scholarly journals β-Cell Knockout of SENP1 Reduces Responses to Incretins and Worsens Oral Glucose Tolerance in High Fat Diet-Fed Mice

Diabetes ◽  
2021 ◽  
pp. db201235
Author(s):  
Haopeng Lin ◽  
Nancy Smith ◽  
Aliya F Spigelman ◽  
Kunimasa Suzuki ◽  
Mourad Ferdaoussi ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
High Fat Diet ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
High Fat ◽  
Β Cell

Chronic high fat feeding and prolonged fasting in liver-specific ANGPTL4 knockout mice

2021 ◽  
Author(s):  
Kathryn Mary Spitler ◽  
Shwetha K Shetty ◽  
Emily M Cushing ◽  
Kelli L. Sylvers-Davie ◽  
Brandon S.J. Davies
Keyword(s):  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
Plasma Triglyceride ◽  
Chow Diet ◽  
Loss Of Function ◽  
High Fat ◽  
Prolonged Fasting ◽  
Normal Chow

Obesity is associated with dyslipidemia, ectopic lipid deposition and insulin resistance. In mice, the global or adipose-specific loss of function of the protein angiopoietin-like 4 (ANGPTL4) leads to decreased plasma triglyceride levels, enhanced adipose triglyceride uptake, and protection from high-fat diet-induced glucose intolerance. ANGPTL4 is also expressed highly in the liver, but the role of liver-derived ANGPTL4 is unclear. The goal of this study was to determine the contribution of hepatocyte ANGPTL4 to triglyceride and glucose homeostasis in mice during a high fat diet challenge. We generated hepatocyte-specific ANGPTL4 deficient (Angptl4LivKO) mice, fed them a 60% kCal/fat diet (HFD) for 6 months, and assessed triglyceride, liver, and glucose metabolic phenotypes. We also explored the effects of prolonged fasting on Angptl4LivKO mice. The loss of hepatocyte-derived Angptl4 led to no major changes in triglyceride partitioning or lipoprotein lipase activity compared to control mice. Interestingly, although there was no difference in fasting plasma triglyceride levels after a 6 h fast, after an 18 h fast normal chow diet fed Angptl4LivKO mice had lower triglyceride levels than control mice. On a HFD, Angptl4LivKO mice initially showed no difference in glucose tolerance and insulin sensitivity, but improved glucose tolerance emerged in these mice after 6 months on HFD. Our data suggest that hepatocyte ANGPTL4 does not directly regulate triglyceride partitioning, but that loss of liver-derived ANGPTL4 may be protective from HFD-induced glucose intolerance and influence plasma TG metabolism during prolonged fasting.

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