Reduction of visceral fat by liraglutide is associated with ameliorations of hepatic steatosis, albuminuria, and micro-inflammation in type 2 diabetic patients with insulin treatment: a randomized control trial

Bouchi, Ryotaro; Nakano, Yujiro; Fukuda, Tatsuya; Takeuchi, Takato; Murakami, Masanori; Minami, Isao; Izumiyama, Hajime; Hashimoto, Kazuhito; Yoshimoto, Takanobu; Ogawa, Yoshihiro

doi:10.1507/endocrj.ej16-0449

Cited by 84 publications

(95 citation statements)

References 40 publications

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“…It has been shown that excessive lipid accumulation within hepatocytes is the main cause to hepatocyte injury characterized by increased ALT and AST concentrations (Magee et al, 2016). Previous studies showed that HFD induced hepatic lipid accumulation was associated with increased liver inflammation, elevated hepatic endoplasmic reticulum stress and activation relevant signaling pathways (Liu et al, 2014), in which the obese-related liver injury could be ameliorated by GLP-1 treatment or therapies using GLP-1 mimetic (Armstrong et al, 2016a,b; Bouchi et al, 2016; He et al, 2016; Valdecantos et al, 2016). …”

Section: Discussionmentioning

confidence: 99%

“…However, the weights of interscapular BAT and inguinal fat were not significantly changed. In general, visceral fat was considered as “bad fat” since it was associated with insulin resistance and increased cardiovascular risk (Hocking et al, 2013; Bouchi et al, 2016). However, subcutaneous fat and BAT were considered as “good fat” given their beneficial effects on the metabolism homeostasis (Hocking et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

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Novel GLP-1 Analog Supaglutide Reduces HFD-Induced Obesity Associated with Increased Ucp-1 in White Adipose Tissue in Mice

et al. 2017

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GLP-1, an important incretin hormone plays an important role in the regulation of glucose homeostasis. However, the therapeutic use of native GLP-1 is limited due to its short half-life. We recently developed a novel GLP-1 mimetics (supaglutide) by genetically engineering recombinant fusion protein production techniques. We demonstrated that this formulation possessed long-lasting GLP-1 actions and was effective in glycemic control in both type 1 and type 2 diabetes rodent models. Here, we investigated the effects of supaglutide in regulating energy homeostasis in obese mice. Mice were fed with high-fat diet (HFD) for 6 months to induce obesity and then subjected to supaglutide treatment (300 μg/kg, bi-weekly for 4 weeks), and placebo as control. Metabolic conditions were monitored and energy expenditure was assessed by indirect calorimetry (CLAMS). Cold tolerance test was performed to evaluate brown-adipose tissue (BAT) activities in response to cold challenge. Glucose tolerance and insulin resistance were evaluated by intraperitoneal glucose tolerance test and insulin tolerance tests. Liver and adipose tissues were collected for histology analysis. Expression of uncoupling protein 1(Ucp1) in adipose tissues was evaluated by Western blotting. We found that supaglutide treatment reduced body weight, which was associated with reduced food intake. Compared to the placebo control, supaglutide treatment improved lipid profile, i.e., significantly decreased circulating total cholesterol levels, declined serum triglyceride, and free fatty acid levels. Importantly, the intervention significantly reduced fatty liver, decreased liver triglyceride content, and concomitantly ameliorated liver injury exemplified by declined hepatic alanine aminotransferase (ALT) and aspartic transaminase (AST) content. Remarkably, supaglutide reduced hepatic lipid accumulation and altered morphometry in favor of small adipocytes in fat. This is consistent with the observation that supaglutide increased tolerance of the mice to cold environment associated with up-regulation of Ucp1 in the inguinal fat. Furthermore, supaglutide improved glucose tolerance, and insulin sensitivity in the obese mice suggesting improved glucose and energy homeostasis. Our findings suggest that supaglutide exerts beneficial effect on established obesity through reducing energy intake and is associated with brown remodeling of white adipose tissue.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Novel GLP-1 Analog Supaglutide Reduces HFD-Induced Obesity Associated with Increased Ucp-1 in White Adipose Tissue in Mice

et al. 2017

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“…Liraglutide is increasingly used for the treatment of type 2 diabetes due to its increased efficiency compared to other treatments in controlling and stabilising glucose plasma level and because of its capacity to reduce both cardiovascular risk and HbA1c (hemoglobin A1C) level (9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Glycation of human serum albumin impairs binding to the glucagon-like peptide-1 analogue liraglutide

Soudahome

Catan

Giraud

et al. 2018

Journal of Biological Chemistry

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“…However, these indices do not allow distinguishing between VAT and subcutaneous abdominal fat and, in general, are fundamentally inaccurate in quantifying VAT [5]. VAT is a relatively small component of total body fat; however, due to known metabolic effects of VAT, there is constantly increasing interest in this fat depot as an attractive target for non-pharmacological [6, 7] and pharmacological interventions [8]. …”

Section: Introductionmentioning

confidence: 99%

Visceral fat reference values derived from healthy European men and women aged 20-30 years using GE Healthcare dual-energy x-ray absorptiometry

et al. 2017

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Dual energy X-ray absorptiometry (DXA) is an established technique used in clinical and research settings to evaluate total and regional fat. Additionally, recently developed software allow to quantify visceral adipose tissue (VAT). Currently, there are no reference values available for GE Healthcare DXA systems for VAT. The aim of this study was to develop reference values for VAT in healthy European adults aged 20–30 years using a GE Healthcare Prodigy densitometer along with the dedicated CoreScan application. We also assessed the associations of VAT with traditional cardiometabolic risk factors. In 421 participants (207 men; 214 women), we performed DXA whole-body scans and calculated total body fat (BF) and VAT (in gender-specific percentiles). We also measured blood pressure and fasting glucose, insulin, and blood lipids. Males, in comparison with females, had 2-fold greater VAT both in units of mass (542 ± 451 g; 95% CI: 479.6‒605.1 g vs. 258 ± 226 g; 95% CI: 226.9‒288.6 g) and volume (570 ± 468 cm3; 95% CI: 505.1‒635.2 cm3 vs. 273 ± 237 cm3; 95% CI: 240.6‒305.3 cm3). They also had significantly higher the VAT/BF ratio. VAT showed a stronger positive correlation than BF with blood pressure, triglycerides, LDL-cholesterol, glucose, insulin, and homeostasis model assessment-insulin resistance index and a stronger negative correlation with HDL-cholesterol. Among these variables, VAT had the highest area under the curve for triglycerides ≥150 mg/dL (0.727 in males and 0.712 in females). In conclusion, we provide reference values for VAT obtained from healthy adults using the GE Healthcare DXA. These values may be useful in the diagnosis of visceral obesity, for identifying subjects with high obesity-related risks, in epidemiological studies, as a target for therapies, and in physically trained individuals. In both genders, VAT was associated with traditional cardiometabolic risk factors, particularly hypertriglyceridemia.

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Reduction of visceral fat by liraglutide is associated with ameliorations of hepatic steatosis, albuminuria, and micro-inflammation in type 2 diabetic patients with insulin treatment: a randomized control trial

Cited by 84 publications

References 40 publications

Novel GLP-1 Analog Supaglutide Reduces HFD-Induced Obesity Associated with Increased Ucp-1 in White Adipose Tissue in Mice

Novel GLP-1 Analog Supaglutide Reduces HFD-Induced Obesity Associated with Increased Ucp-1 in White Adipose Tissue in Mice

Glycation of human serum albumin impairs binding to the glucagon-like peptide-1 analogue liraglutide

Visceral fat reference values derived from healthy European men and women aged 20-30 years using GE Healthcare dual-energy x-ray absorptiometry

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