Translating Animal Models of Obesity and Diabetes to the Clinic

Author(s):  
B.M. Geiger ◽  
E.N. Pothos
2009 ◽  
Vol 297 (3) ◽  
pp. E657-E664 ◽  
Author(s):  
Ying Liu ◽  
Simon Chewchuk ◽  
Charles Lavigne ◽  
Sophie Brûlé ◽  
Genevieve Pilon ◽  
...  

Endocrine effects of adipose-derived adiponectin on skeletal muscle have been shown to account, at least in part, for the anti-diabetic effects of this adipokine. Recently, the concept of myokines has gained credence, and the potential for skeletal muscle to produce adiponectin has been suggested. Here we demonstrated an increased level of adiponectin mRNA and protein expression as well as protein secretion in response to rosiglitazone treatment in L6 muscle cells. This correlated with the ability of rosiglitazone to enhance insulin sensitivity for stimulation of protein kinase B (Akt) phosphorylation and glucose transport; rosiglitazone also corrected high-glucose-induced insulin resistance in L6 cells. Overexpression of adiponectin confirmed the functional significance of local production of adiponectin in muscle cells via elevated glucose uptake and increased insulin sensitivity. In obese diabetic db/db mice, there was a change in the adiponectin expression profile in soleus and extensor digitorum longus (EDL) muscle with less high molecular weight (HMW) and more medium (MMW)/low (LMW) molecular weight species detected. Induction of obesity and insulin resistance in rats by feeding a high-fat high-sucrose diet also led to decreased muscle HMW adiponectin content that could be corrected by rosiglitazone treatment. In summary, we show the ability of skeletal muscle cells to produce adiponectin, which can mediate autocrine metabolic effects, thus establishing adiponectin as a bona fide myokine. We also demonstrate that skeletal muscle adiponectin production is altered in animal models of obesity and diabetes and that these changes can be corrected by rosiglitazone.


Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4394 ◽  
Author(s):  
Kitamura

Propolis is a natural product resulting from the mixing of bee secretions with botanical exudates. Since propolis is rich in flavonoids and cinnamic acid derivatives, the application of propolis extracts has been tried in therapies against cancer, inflammation, and metabolic diseases. As metabolic diseases develop relatively slowly in patients, the therapeutic effects of propolis in humans should be evaluated over long periods of time. Moreover, several factors such as medical history, genetic inheritance, and living environment should be taken into consideration in human studies. Animal models, especially mice and rats, have some advantages, as genetic and microbiological variables can be controlled. On the other hand, cellular models allow the investigation of detailed molecular events evoked by propolis and derivative compounds. Taking advantage of animal and cellular models, accumulating evidence suggests that propolis extracts have therapeutic effects on obesity by controlling adipogenesis, adipokine secretion, food intake, and energy expenditure. Studies in animal and cellular models have also indicated that propolis modulates oxidative stress, the accumulation of advanced glycation end products (AGEs), and adipose tissue inflammation, all of which contribute to insulin resistance or defects in insulin secretion. Consequently, propolis treatment may mitigate diabetic complications such as nephropathy, retinopathy, foot ulcers, and non-alcoholic fatty liver disease. This review describes the beneficial effects of propolis on metabolic disorders.


2006 ◽  
Vol 967 (1) ◽  
pp. 403-413 ◽  
Author(s):  
GREG COLLIER ◽  
KEN WALDER ◽  
ANDREA SILVA ◽  
JANETTE TENNE-BROWN ◽  
ANDREW SANIGORSKI ◽  
...  

2021 ◽  
pp. 108923
Author(s):  
Maya Faour ◽  
Christophe Magnan ◽  
Hirac Gurden ◽  
Claire Martin

2018 ◽  
Vol 14 (3) ◽  
pp. 140-162 ◽  
Author(s):  
Maximilian Kleinert ◽  
Christoffer Clemmensen ◽  
Susanna M. Hofmann ◽  
Mary C. Moore ◽  
Simone Renner ◽  
...  

2019 ◽  
Author(s):  
Julia Rogal ◽  
Carina Binder ◽  
Elena Kromidas ◽  
Christopher Probst ◽  
Stefan Schneider ◽  
...  

AbstractObesity and its numerous adverse health consequences have taken on global, pandemic proportions. White adipose tissue (WAT) – a key contributor in many metabolic diseases – contributes about one fourth of a healthy human’s body mass. Despite its significance, many WAT-related pathophysiogical mechanisms in humans are still not understood, largely due to the reliance on non-human animal models. In recent years, Organ-on-a-chip (OoC) platforms have developed into promising alternatives for animal models; these systems integrate engineered human tissues into physiological microenvironment supplied by a vasculature-like microfluidic perfusion. Here, we report the development of a novel OoC that integrates functional mature human WAT. The WAT-on-a-chip is a multilayer device that features tissue chambers tailored specifically for the maintenance of 3D tissues based on human primary adipocytes, with supporting nourishment provided through perfused media channels. The platform’s capability to maintain long-term viability and functionality of WAT was confirmed by real-time monitoring of fatty acid uptake, by quantification of metabolite release into the effluent media as well as by an intact responsiveness to a therapeutic compound. The novel system provides a promising tool for wide-ranging applications in mechanistic research of WAT-related biology, in studying of pathophysiological mechanisms in obesity and diabetes, and in R&D of pharmaceutical industry.


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