scholarly journals 40 YEARS of IGF1: Understanding the tissue-specific roles of IGF1/IGF1R in regulating metabolism using the Cre/loxP system

2018 ◽  
Vol 61 (1) ◽  
pp. T187-T198 ◽  
Author(s):  
Rhonda D Kineman ◽  
Mercedes del Rio-Moreno ◽  
André Sarmento-Cabral

It is clear that insulin-like growth factor-1 (IGF1) is important in supporting growth and regulating metabolism. The IGF1 found in the circulation is primarily produced by the liver hepatocytes, but healthy mature hepatocytes do not express appreciable levels of the IGF1 receptor (IGF1R). Therefore, the metabolic actions of IGF1 are thought to be mediated via extra-hepatocyte actions. Given the structural and functional homology between IGF1/IGF1R and insulin receptor (INSR) signaling, and the fact that IGF1, IGF1R and INSR are expressed in most tissues of the body, it is difficult to separate out the tissue-specific contributions of IGF1/IGF1R in maintaining whole body metabolic function. To circumvent this problem, over the last 20 years, investigators have taken advantage of the Cre/loxP system to manipulate IGF1/IGF1R in a tissue-dependent, and more recently, an age-dependent fashion. These studies have revealed that IGF1/IGF1R can alter extra-hepatocyte function to regulate hormonal inputs to the liver and/or alter tissue-specific carbohydrate and lipid metabolism to alter nutrient flux to liver, where these actions are not mutually exclusive, but serve to integrate the function of all tissues to support the metabolic needs of the organism.

2011 ◽  
Vol 106 (5) ◽  
pp. 633-647 ◽  
Author(s):  
Bente E. Torstensen ◽  
Marit Espe ◽  
Ingunn Stubhaug ◽  
Øyvind Lie

In order to study whether lipid metabolism may be affected by maximum replacement of dietary fish oil and fish meal with vegetable oils (VO) and plant proteins (PP), Atlantic salmon (Salmo salarL.) smolts were fed a control diet containing fish oil and fish meal or one of three plant-based diets through the seawater production phase for 12 months. Diets were formulated to meet all known nutrient requirements. The whole-body lipid storage pattern was measured after 12 months, as well as post-absorptive plasma, VLDL and liver TAG. To further understand the effects on lipid metabolism, expression of genes encoding for proteins involved in VLDL assembly (apoB100), fatty acid uptake (FATP1, cd36, LPL and FABP3, FABP10 and FABP11) were measured in liver and visceral adipose tissue. Maximum dietary VO and PP increased visceral lipid stores, liver TAG, and plasma VLDL and TAG concentrations. Increased plasma TAG correlated with an increased expression of apoB100, indicating increased VLDL assembly in the liver of fish fed the high-plant protein- and VO-based diet. Atlantic salmon fed intermediate replacement levels of VO or PP did not have increased body fat or visceral mass. Overall, the present results demonstrate an interaction between dietary lipids and protein on lipid metabolism, increasing overall adiposity and TAG in the body when fish meal and fish oil are replaced concomitantly at maximised levels of VO and PP.


2020 ◽  
Vol 103 (6) ◽  
pp. 1199-1208
Author(s):  
Menliang Zhu ◽  
Qiyang Shen ◽  
Xiaolian Li ◽  
Jihong Kang

Abstract The development and maturity of follicles are regulated by sex hormones and growth factors. It has been proven that peri-ovarian adipose tissue (POAT) plays an important role in folliculogenesis and fertility in the female ICR and KM mice. The aim of the present study was to further investigate whether the removal of bilateral POAT affected follicular development and lipid metabolism in the female C57BL/6 J mice. Female C57BL/6 J mice at 6-week old were sham-operated (Sham) or removed bilateral POAT (Surgery). After 2 weeks, the mice were subjected to the body composition analysis and indirect calorimetry measurement. Our results show that the Surgery mice exhibited abnormal follicular development, including increased follicular dysplasia and atresia, decreased serum sex hormone levels, and abnormal expression of follicular development-related genes. Correspondingly, the endometrial thickness of the Surgery mice was less than the Sham mice. In addition, the Surgery mice had abnormal lipid metabolism, including reduced fat mass, increased energy expenditure, and up-regulated gene and protein expression involved in lipolysis. These data confirmed the importance of POAT in the follicular development in the female reproduction and suggested the contribution of POAT to the whole-body lipid metabolism.


Author(s):  
Sandra F. Gallego ◽  
Richard R. Sprenger ◽  
Ditte Neess ◽  
Josch K. Pauling ◽  
Nils J. Færgeman ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Taylor Landry ◽  
Daniel Shookster ◽  
Hu Huang

Rho-kinase 1 (ROCK1) has been implicated in diverse metabolic functions throughout the body, with promising evidence identifying ROCK1 as a therapeutic target in diabetes and obesity. Considering these metabolic roles, several pharmacological inhibitors have been developed to elucidate the mechanisms underlying ROCK1 function. Y27632 and fasudil are two common ROCK1 inhibitors; however, they have varying non-specific selectivity to inhibit other AGC kinase subfamily members and whole-body pharmacological approaches lack tissue-specific insight. As a result, interpretation of studies with these inhibitors is difficult, and alternative approaches are needed to elucidate ROCK1’s tissue specific metabolic functions. Fortunately, recent technological advances utilizing molecular carriers or genetic manipulation have facilitated discovery of ROCK1’s tissue-specific mechanisms of action. In this article, we review the tissue-specific roles of ROCK1 in the regulation of energy balance and substrate utilization. We highlight prominent metabolic roles in liver, adipose, and skeletal muscle, in which ROCK1 regulates energy expenditure, glucose uptake, and lipid metabolism via inhibition of AMPK2α and paradoxical modulation of insulin signaling. Compared to ROCK1’s roles in peripheral tissues, we also describe contradictory functions of ROCK1 in the hypothalamus to increase energy expenditure and decrease food intake via leptin signaling. Furthermore, dysregulated ROCK1 activity in either of these tissues results in metabolic disease phenotypes. Overall, tissue-specific approaches have made great strides in deciphering the many critical metabolic functions of ROCK1 and, ultimately, may facilitate the development of novel treatments for metabolic disorders.


1985 ◽  
Vol 54 (2) ◽  
pp. 401-413 ◽  
Author(s):  
Susan J. Fairweather-Tait ◽  
A. J. A. Wright ◽  
Jacqui Cooke ◽  
J. Franklin

1. The metabolism of 65Zn administered intramuscularly (Expt 1) or enterally (Expt 2) at the beginning of pregnancy in rats given a control or marginal-Zn diet was measured. In Expt 2 a comparison was also made between pregnant and non-pregnant rats. The loss of 65Zn (assumed to represent labile body Zn) was markedly reduced in animals fed on a marginal-Zn diet compared with controls, and this effect occurred very rapidly, i.e. within 48 h of introducing the marginal-Zn diet. Pregnancy itself had a much less important effect on 65Zn turnover than diet. Transfer of 65Zn to the litter was significantly greater in the animals fed on a marginal-Zn diet compared with controls but total Zn transfer was reduced.2. The effect of length of time on a marginal-Zn diet on fetal growth and composition was examined. Compared with controls, fetal weight was significantly greater in litters from mothers fed on a marginal-Zn diet during the last 4, 7 or 14 d of pregnancy, but no different in litters from mothers fed on a marginal-Zn diet throughout pregnancy. There were no differences in the proportions of protein or fat in the fetuses from mothers fed on the control or marginal-Zn diets but the Zn concentration was lower in litters from mothers fed on a marginal-Zn diet during part or ail of the pregnancy when compared with controls.3. The transfer of 65Zn from mothers to litters during birth and the first 3 d of lactation was measured. There were no differences in maternal or litter 65Zn just before or just after birth, but within 72 h maternal 65Zn had significantly decreased and litter 65Zn increased. Increases in litter size were associated with greater total litter 65Zn but reduced individual fetal 65Zn.4. These experiments demonstrate the importance of an adequate daily supply of Zn during pregnancy. Although there is room for adaptation to a marginal-Zn intake (by reducing Zn excretion) the maintenance of Zn homeostasis is only possible in the absence of other forms of stress, such as pregnancy, to the body. The consequence of insufficient Zn at times of rapid fetal growth on carbohydrate and lipid metabolism warrants further investigation.


1976 ◽  
Vol 15 (05) ◽  
pp. 248-253
Author(s):  
A. K. Basu ◽  
S. K. Guha ◽  
B. N. Tandon ◽  
M. M. Gupta ◽  
M. ML. Rehani

SummaryThe conventional radioisotope scanner has been used as a whole body counter. The background index of the system is 10.9 counts per minute per ml of sodium iodide crystal. The sensitivity and derived sensitivity parameters have been evaluated and found to be suitable for clinical studies. The optimum parameters for a single detector at two positions above the lying subject have been obtained. It has been found that for the case of 131I measurement it is possible to assay a source located at any point in the body with coefficient of variation less than 5%. To add to the versatility, a fixed geometry for in-vitro counting of large samples has been obtained. The retention values obtained by the whole body counter have been found to correlate with those obtained by in-vitro assay of urine and stool after intravenous administration of 51Cr-albumin.


Author(s):  
Kashish Narula ◽  
Narendra Kumar Dara ◽  
Shyam Lal Meena

Background: Thyroid hormones influence nearly all major metabolic pathways. Their most obvious and well-known action is the increase in basal energy expenditure obtained by acting on protein, carbohydrate and lipid metabolism. The lipid metabolism is more influenced by the thyroid hormone. Methods: A cross-sectional study was conducted on 100 patients with suspicion of thyroid disorders were taken as cases. One hundred patients with normal thyroid profile and no history of other chronic diseases were taken as control group. Results: The serum TC, TG and LDL levels in hypothyroid individuals (both overt and subclinical) were significantly higher than euthyroid subjects but the levels were comparable between hyperthyroid and euthyroid group. Conclusion: Dyslipidemias are associated with thyroid disorders, so biochemical screening for thyroid dysfunction in all dyslipidemic patients. Therefore, patients presenting with dyslipidemia are recommended for investigation to explore thyroid dysfunction. Keywords: Thyroid profile, Total cholesterol, Triglycerides and LDL


2008 ◽  
Vol 396-398 ◽  
pp. 569-572
Author(s):  
Fumio Watari ◽  
Shigeaki Abe ◽  
I.D. Rosca ◽  
Atsuro Yokoyama ◽  
Motohiro Uo ◽  
...  

Nanoparticles may invade directly into the internal body through the respiratory or digestive system and diffuse inside body. The behavior of nanoparticles in the internal body is also essential to comprehend for the realization of DDS. Thus it is necessary to reveal the internal dynamics for the proper treatments and biomedical applications of nanoparticles. In the present study the plural methods with different principles such as X-ray scanning analytical microscope (XSAM), MRI and Fluorescent microscopy were applied to enable the observation of the internal diffusion of micro/nanoparticles in the (1) whole body level, (2) inner organ level and (3) tissue and intracellular level. Chemical analysis was also done by ICP-AES for organs and compared with the results of XSAM mapping.


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