scholarly journals Hypoxia exposure alleviates impaired muscular metabolism, glucose tolerance, and aerobic capacity in apelin‐knockout mice

FEBS Open Bio ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 498-509 ◽  
Author(s):  
Shiyi He ◽  
Junping Li ◽  
Jianxiong Wang ◽  
Ying Zhang
Keyword(s):  
Glucose Tolerance ◽  
Aerobic Capacity ◽  
Knockout Mice ◽  
Hypoxia Exposure ◽  
Muscular Metabolism

scholarly journals Minimal impact of age and housing temperature on the metabolic phenotype of Acc2−/− mice

2015 ◽  
Vol 228 (3) ◽  
pp. 127-134 ◽  
Author(s):  
Amanda E Brandon ◽  
Ella Stuart ◽  
Simon J Leslie ◽  
Kyle L Hoehn ◽  
David E James ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Composition ◽  
Energy Expenditure ◽  
Glucose Tolerance ◽  
Fat Mass ◽  
Knockout Mice ◽  
Muscle Glycogen ◽  
Insulin Action ◽  
Metabolic Phenotype ◽  
Whole Body

An important regulator of fatty acid oxidation (FAO) is the allosteric inhibition of CPT-1 by malonyl-CoA produced by the enzyme acetyl-CoA carboxylase 2 (ACC2). Initial studies suggested that deletion of Acc2 (Acacb) increased fat oxidation and reduced adipose tissue mass but in an independently generated strain of Acc2 knockout mice we observed increased whole-body and skeletal muscle FAO and a compensatory increase in muscle glycogen stores without changes in glucose tolerance, energy expenditure or fat mass in young mice (12–16 weeks). The aim of the present study was to determine whether there was any effect of age or housing at thermoneutrality (29 °C; which reduces total energy expenditure) on the phenotype of Acc2 knockout mice. At 42–54 weeks of age, male WT and Acc2−/− mice had similar body weight, fat mass, muscle triglyceride content and glucose tolerance. Consistent with younger Acc2−/− mice, aged Acc2−/− mice showed increased whole-body FAO (24 h average respiratory exchange ratio=0.95±0.02 and 0.92±0.02 for WT and Acc2−/− mice respectively, P<0.05) and skeletal muscle glycogen content (+60%, P<0.05) without any detectable change in whole-body energy expenditure. Hyperinsulinaemic–euglycaemic clamp studies revealed no difference in insulin action between groups with similar glucose infusion rates and tissue glucose uptake. Housing Acc2−/− mice at 29 °C did not alter body composition, glucose tolerance or the effects of fat feeding compared with WT mice. These results confirm that manipulation of Acc2 may alter FAO in mice, but this has little impact on body composition or insulin action.

scholarly journals The depot-specific and essential roles of CBP/p300 in regulating adipose plasticity

2019 ◽  
Vol 240 (2) ◽  
pp. 257-269 ◽  
Author(s):  
Maria Namwanje ◽  
Longhua Liu ◽  
Michelle Chan ◽  
Nikki Aaron ◽  
Michael J Kraakman ◽  
...  
Keyword(s):  
Body Weight ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Knockout Mice ◽  
Metabolic Disorders ◽  
Physiological Effects ◽  
Double Knockout ◽  
Adipose Tissues ◽  
Diet Induced Obesity ◽  
Specific Deletion

Fat remodeling has been extensively explored through protein deacetylation, but not yet acetylation, as a viable therapeutic approach in the management of obesity and related metabolic disorders. Here, we investigated the functions of key acetyltransferases CBP/p300 in adipose remodeling and their physiological effects by generating adipose-specific deletion of CBP (Cbp-AKO), p300 (p300-AKO) and double-knockout (Cbp/p300-AKO) models. We demonstrated that Cbp-AKO exhibited marked brown remodeling of inguinal WAT (iWAT) but not epididymal WAT (eWAT) after cold exposure and that this pattern was exaggerated in diet-induced obesity (DIO). Despite this striking browning phenotype, loss of Cbp was insufficient to impact body weight or glucose tolerance. In contrast, ablation of p300 in adipose tissues had minimal effects on fat remodeling and adiposity. Surprisingly, double-knockout mice (Cbp/p300-AKO) developed severe lipodystrophy along with marked hepatic steatosis, hyperglycemia and hyperlipidemia. Furthermore, we demonstrated that pharmacological inhibition of Cbp and p300 activity suppressed adipogenesis. Collectively, these data suggest that (i) CBP, but not p300, has distinct functions in regulating fat remodeling and that this occurs in a depot-selective manner; (ii) brown remodeling occurs independently of the improvements in glucose metabolism and obesity and (iii) the combined roles of CBP and p300 are indispensable for normal adipose development.

scholarly journals Nordic Walking Promoted Weight Loss in Overweight and Obese People: A Systematic Review for Future Exercise Prescription

2019 ◽  
Vol 4 (2) ◽  
pp. 36 ◽  
Author(s):  
Stefano Gobbo ◽  
Valentina Bullo ◽  
Enrico Roma ◽  
Federica Duregon ◽  
Danilo Sales Bocalini ◽  
...  
Keyword(s):  
Systematic Review ◽  
Weight Loss ◽  
Body Composition ◽  
Glucose Tolerance ◽  
Blood Sample ◽  
Aerobic Capacity ◽  
Nordic Walking ◽  
Anthropometric Parameters ◽  
Obese People ◽  
Cardiovascular Parameters

The aim of this systematic review was to analyze the effect of Nordic Walking (NW) on anthropometric parameters, body composition, cardiovascular parameters, aerobic capacity, blood sample, and glucose tolerance in overweight and obese subjects. The main keywords “Nordic Walking” or “Pole Walking”, associated with either “obese”, “obesity”, “overweight”, or “weight loss” were used on the online database MEDLINE, PubMed, SPORTDiscus and Scopus. Additionally, references of the studies included were screened to identify eligible articles. Applying the inclusion and exclusion criteria, ten manuscripts were considered as eligible for this review. The results of the studies were categorized in several domains with regard to “anthropometric parameters and body composition”, “cardiovascular parameters and aerobic capacity”, and “blood sample and glucose tolerance”. The results showed positive effects on the anthropometric parameters, body composition, cardiovascular parameters, blood sample, and glucose tolerance. The greatest improvements were observed in supervised and high weekly frequency of NW interventions. NW could be considered as an effective modality through which to involve the obese in physical activity. For weight loss, NW should be prescribed 4–5 times per week, at least 60 min per session, preferably combined with diet control.

Strength training improves muscle aerobic capacity and glucose tolerance in elderly

2015 ◽  
Vol 26 (7) ◽  
pp. 764-773 ◽  
Author(s):  
P. Frank ◽  
E. Andersson ◽  
M. Pontén ◽  
B. Ekblom ◽  
M. Ekblom ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Strength Training ◽  
Aerobic Capacity

scholarly journals Tpcn2 knockout mice have improved insulin sensitivity and are protected against high-fat diet-induced weight gain

2018 ◽  
Vol 50 (8) ◽  
pp. 605-614
Author(s):  
Hong He ◽  
Katie Holl ◽  
Sarah DeBehnke ◽  
Chay Teng Yeo ◽  
Polly Hansen ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Wild Type ◽  
High Fat ◽  
Male And Female ◽  
Female Mice

Type 2 diabetes is a complex disorder affected by multiple genes and the environment. Our laboratory has shown that in response to a glucose challenge, two-pore channel 2 ( Tpcn2) knockout mice exhibit a decreased insulin response but normal glucose clearance, suggesting they have improved insulin sensitivity compared with wild-type mice. We tested the hypothesis that improved insulin sensitivity in Tpcn2 knockout mice would protect against the negative effects of a high fat diet. Male and female Tpcn2 knockout (KO), heterozygous (Het), and wild-type (WT) mice were fed a low-fat (LF) or high-fat (HF) diet for 24 wk. HF diet significantly increases body weight in WT mice relative to those on the LF diet; this HF diet-induced increase in body weight is blunted in the Het and KO mice. Despite the protection against diet-induced weight gain, however, Tpcn2 KO mice are not protected against HF-diet-induced changes in glucose or insulin area under the curve during glucose tolerance tests in female mice, while HF diet has no significant effect on glucose tolerance in the male mice, regardless of genotype. Glucose disappearance during an insulin tolerance test is augmented in male KO mice, consistent with our previous findings suggesting enhanced insulin sensitivity in these mice. Male KO mice exhibit increased fasting plasma total cholesterol and triglyceride concentrations relative to WT mice on the LF diet, but this difference disappears in HF diet-fed mice where there is increased cholesterol and triglycerides across all genotypes. These data demonstrate that knockout of Tpcn2 may increase insulin action in male, but not female, mice. In addition, both male and female KO mice are protected against diet-induced weight gain, but this protection is likely independent from glucose tolerance, insulin sensitivity, and plasma lipid levels.

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 Disruption of Phospholipid Transfer Protein–Mediated High-Density Lipoprotein Maturation Reduces Scavenger Receptor BI Deficiency–Driven Atherosclerosis Susceptibility Despite Unexpected Metabolic Complications

2020 ◽  
Vol 40 (3) ◽  
pp. 611-623 ◽  
Author(s):  
Menno Hoekstra ◽  
Ronald J. van der Sluis ◽  
Reeni B. Hildebrand ◽  
Bart Lammers ◽  
Ying Zhao ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Knockout Mice ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Phospholipid Transfer Protein ◽  
Double Knockout ◽  
Metabolic Complications ◽  
Scavenger Receptor Bi ◽  
Transfer Protein ◽  
Phospholipid Transfer

Objective: We tested the hypothesis that enlarged, dysfunctional HDL (high-density lipoprotein) particles contribute to the augmented atherosclerosis susceptibility associated with SR-BI (scavenger receptor BI) deficiency in mice. Approach and Results: We eliminated the ability of HDL particles to fully mature by targeting PLTP (phospholipid transfer protein) functionality. Particle size of the HDL population was almost fully normalized in male and female SR-BI×PLTP double knockout mice. In contrast, the plasma unesterified cholesterol to cholesteryl ester ratio remained elevated. The PLTP deficiency-induced reduction in HDL size in SR-BI knockout mice resulted in a normalized aortic tissue oxidative stress status on Western-type diet. Atherosclerosis susceptibility was—however—only partially reversed in double knockout mice, which can likely be attributed to the fact that they developed a metabolic syndrome-like phenotype characterized by obesity, hypertriglyceridemia, and a reduced glucose tolerance. Mechanistic studies in chow diet–fed mice revealed that the diminished glucose tolerance was probably secondary to the exaggerated postprandial triglyceride response. The absence of PLTP did not affect LPL (lipoprotein lipase)-mediated triglyceride lipolysis but rather modified the ability of VLDL (very low-density lipoprotein)/chylomicron remnants to be cleared from the circulation by the liver through receptors other than SR-BI. As a result, livers of double knockout mice only cleared 26% of the fractional dose of [ 14 C]cholesteryl oleate after intravenous VLDL-like particle injection. Conclusions: We have shown that disruption of PLTP-mediated HDL maturation reduces SR-BI deficiency-driven atherosclerosis susceptibility in mice despite the induction of proatherogenic metabolic complications in the double knockout mice.

Improved blood glucose disposal and altered insulin secretion patterns in adenosine A1 receptor knockout mice

2012 ◽  
Vol 303 (2) ◽  
pp. E180-E190 ◽  
Author(s):  
Gary K. Yang ◽  
Bertil B. Fredholm ◽  
Timothy J. Kieffer ◽  
Yin Nam Kwok
Keyword(s):  
Glucose Tolerance ◽  
Insulin Release ◽  
Knockout Mice ◽  
The Body ◽  
Glucose Disposal ◽  
Wild Type ◽  
Β Cells ◽  
Pancreas Perfusion ◽  
Glucose Levels ◽  
Glucose Challenge

Type 2 diabetes mellitus (T2DM) is characterized by the inability of the pancreatic β-cells to secrete enough insulin to meet the demands of the body. Therefore, research of potential therapeutic approaches to treat T2DM has focused on increasing insulin output from β-cells or improving systemic sensitivity to circulating insulin. In this study, we examined the role of the A1 receptor in glucose homeostasis with the use of A1 receptor knockout mice (A1R−/−). A1R−/− mice exhibited superior glucose tolerance compared with wild-type controls. However, glucose-stimulated insulin release, insulin sensitivity, weight gain, and food intake were comparable between the two genotypes. Following a glucose challenge, plasma glucagon levels in wild-type controls decreased, but this was not observed in A1R−/− mice. In addition, pancreas perfusion with oscillatory glucose levels of 10-min intervals produced a regular pattern of pulsatile insulin release with a 10-min cycling period in wild-type controls and 5 min in A1R−/− mice. When the mice were fed a high-fat diet (HFD), both genotypes exhibited impaired glucose tolerance and insulin resistance. Increased insulin release was observed in HFD-fed mice in both genotypes, but increased glucagon release was observed only in HFD-fed A1R−/− mice. In addition, the regular patterns of insulin release following oscillatory glucose perfusion were abolished in HFD-fed mice in both genotypes. In conclusion, A1 receptors in the pancreas are involved in regulating the temporal patterns of insulin release, which could have implications in the development of glucose intolerance seen in T2DM.

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