scholarly journals Analysis of the SYSDIET Healthy Nordic Diet randomized trial based on metabolic profiling reveal beneficial effects on glucose metabolism and blood lipids

Author(s):  
Gözde Gürdeniz ◽  
Matti Uusitupa ◽  
Kjeld Hermansen ◽  
Markku J. Savolainen ◽  
Ursula Schwab ◽  
...  
2021 ◽  
Author(s):  
Carmelo Quarta ◽  
Kerstin Stemmer ◽  
Aaron Novikoff ◽  
Bin Yang ◽  
Felix Klingelhuber ◽  
...  

Abstract Dual-agonists activating the peroxisome proliferator-activated receptors alpha and gamma (PPAR𝛼/𝛾) have shown beneficial effects on glucose and lipid metabolism in patients with type 2 diabetes, but their development was discontinued due to unfavorable cardiovascular and/or renal effects. Here we report the design and preclinical evaluation of a molecule that covalently links the PPAR𝛼/𝛾 dual-agonist Tesaglitazar to GLP-1 to allow for the GLP-1 receptor-dependent delivery of Tesaglitazar. GLP-1/Tesaglitazar does not differ from matched GLP-1 in GLP-1R signaling, but shows GLP-1R-dependent PPAR𝛾-RXR heterodimerization with enhanced efficacy to improve body weight, food intake, and glucose metabolism relative to GLP-1 or Tesaglitazar in mice with diet- and genetically-induced obesity. The conjugate fails to affect body weight and glucose metabolism in GLP-1R knockout (ko) mice and shows preserved effects in DIO mice at doses subthreshold for GLP-1 and Tesaglitazar to improve metabolism. Consistent with the GLP-1R expression pattern, LC/MS-based proteomics identified a series of novel PPAR protein targets in the hypothalamus that are acutely upregulated by Tesaglitazar and by GLP-1/Tesaglitazar, but not by treatment with GLP-1. Collectively, our data show that GLP-1/Tesaglitazar improves energy and glucose metabolism with superior efficacy to GLP-1 or Tesaglitazar alone and suggest that this conjugate holds therapeutic value to treat hyperglycemia and insulin resistance.


Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2139
Author(s):  
Paulina Wasserfurth ◽  
Josefine Nebl ◽  
Jan Philipp Schuchardt ◽  
Mattea Müller ◽  
Tim Konstantin Boßlau ◽  
...  

Aging is accompanied by a progressive decline in muscle mass and an increase in fat mass, which are detrimental changes associated with the development of health conditions such as type-2 diabetes mellitus or chronic low-grade inflammation. Although both exercise as well as nutritional interventions are known to be beneficial in counteracting those age-related changes, data to which extent untrained elderly people may benefit is still sparse. Therefore, a randomized, controlled, 12-week interventional trial was conducted in which 134 healthy untrained participants (96 women and 38 men, age 59.4 ± 5.6 years, body mass index (BMI) 28.4 ± 5.8 kg/m2) were allocated to one of four study groups: (1) control group with no intervention (CON); (2) 2×/week aerobic and resistance training only (EX); (3) exercise routine combined with dietary counseling in accordance with the guidelines of the German Nutrition Society (EXDC); (4) exercise routine combined with intake of 2 g/day oil from Calanus finmarchicus (EXCO). Body composition (bioelectrical impedance analysis), as well as markers of glucose metabolism and blood lipids, were analyzed at the beginning and the end of the study. The highest decreases in body fat were observed within the EXCO group (−1.70 ± 2.45 kg, p < 0.001), and the EXDC (−1.41 ± 2.13 kg, p = 0.008) group. Markers of glucose metabolism and blood lipids remained unchanged in all groups. Taken together results of this pilot study suggest that a combination of moderate exercise and intake of oil from Calanus finmarchicus or a healthy diet may promote fat loss in elderly untrained overweight participants.


2020 ◽  
Vol 133 (7) ◽  
pp. 863-867
Author(s):  
Jia Zheng ◽  
Li-Yuan Zhou ◽  
Xin-Hua Xiao

1994 ◽  
Vol 23 (4) ◽  
pp. 943-950 ◽  
Author(s):  
Michael L. Fisher ◽  
Stephen S. Gottlieb ◽  
Gary D. Plotnick ◽  
Nancy L. Greenberg ◽  
Richard D. Patten ◽  
...  

2016 ◽  
Vol 229 (2) ◽  
pp. R57-R66 ◽  
Author(s):  
Antonella Amato ◽  
Sara Baldassano ◽  
Flavia Mulè

Glucagon-like peptide 2 (GLP2) is a proglucagon-derived peptide produced by intestinal enteroendocrine L-cells and by a discrete population of neurons in the brainstem, which projects mainly to the hypothalamus. The main biological actions of GLP2 are related to the regulation of energy absorption and maintenance of mucosal morphology, function and integrity of the intestine; however, recent experimental data suggest that GLP2 exerts beneficial effects on glucose metabolism, especially in conditions related to increased uptake of energy, such as obesity, at least in the animal model. Indeed, mice lacking GLP2 receptor selectively in hypothalamic neurons that express proopiomelanocortin show impaired postprandial glucose tolerance and hepatic insulin resistance (by increased gluconeogenesis). Moreover, GLP2 acts as a beneficial factor for glucose metabolism in mice with high-fat diet-induced obesity. Thus, the aim of this review is to update and summarize current knowledge about the role of GLP2 in the control of glucose homeostasis and to discuss how this molecule could exert protective effects against the onset of related obesity type 2 diabetes.


Obesity ◽  
2011 ◽  
Vol 19 (6) ◽  
pp. 1200-1204 ◽  
Author(s):  
Kevin B. Comerford ◽  
Joseph D. Artiss ◽  
K.-L. Catherine Jen ◽  
Sidika E. Karakas

2015 ◽  
Vol 113 (3) ◽  
pp. 383-402 ◽  
Author(s):  
Trudy Voortman ◽  
Anna Vitezova ◽  
Wichor M. Bramer ◽  
Charlotte L. Ars ◽  
Paula K. Bautista ◽  
...  

High protein intake in early childhood is associated with obesity, suggesting possible adverse effects on other cardiometabolic outcomes. However, studies in adults have suggested beneficial effects of protein intake on blood pressure (BP) and lipid profile. Whether dietary protein intake is associated with cardiovascular and metabolic health in children is unclear. Therefore, we aimed to systematically review the evidence on the associations of protein intake with BP, insulin sensitivity and blood lipids in children. We searched the databases Medline, Embase, Cochrane Central and PubMed for interventional and observational studies in healthy children up to the age of 18 years, in which associations of total, animal and/or vegetable protein intake with one or more of the following outcomes were reported: BP; measures of insulin sensitivity; cholesterol levels; or TAG levels. In the search, we identified 6636 abstracts, of which fifty-six studies met all selection criteria. In general, the quality of the included studies was low. Most studies were cross-sectional, and many did not control for potential confounders. No overall associations were observed between protein intake and insulin sensitivity or blood lipids. A few studies suggested an inverse association between dietary protein intake and BP, but evidence was inconclusive. Only four studies examined the effects of vegetable or animal protein intake, but with inconsistent results. In conclusion, the literature, to date provides insufficient evidence for effects of protein intake on BP, insulin sensitivity or blood lipids in children. Future studies could be improved by adequately adjusting for key confounders such as energy intake and obesity.


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