High‐fat diet increases IGF‐I activity in skeletal growth plates before the onset of obesity

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Allison L. Machnicki ◽  
Cassaundra A. Song ◽  
Sarah Evans ◽  
Chad A. Meadows ◽  
Darby McCloud ◽  
...  
Author(s):  
Allison L. Machnicki ◽  
Cassaundra A. White ◽  
Chad A. Meadows ◽  
Darby McCloud ◽  
Sarah Evans ◽  
...  

Nearly one-third of children in the United States are overweight or obese by their pre-teens. Tall stature and accelerated bone elongation are characteristic features of childhood obesity, which co-occur with conditions such as limb bowing, slipped epiphyses, and fractures. Obese children paradoxically have normal circulating IGF-I, the major growth-stimulating hormone. Here we describe and validate a mouse model of excess dietary fat to examine mechanisms of growth acceleration in obesity. We used in vivo multiphoton imaging and immunostaining to test the hypothesis that high-fat diet increases IGF-I activity and alters growth plate structure before the onset of obesity. We tracked bone and body growth in male and female C57BL/6 mice (N = 114) on high-fat (60% kcal fat) or control (10% kcal fat) diets from weaning (3-weeks) to skeletal maturity (12-weeks). Tibial and tail elongation rates increased after brief (1-2 week) high-fat diet exposure without altering serum IGF-I. Femoral bone density and growth plate size were increased, but growth plates were disorganized in not-yet-obese high-fat diet mice. Multiphoton imaging revealed more IGF-I in the vasculature surrounding growth plates of high-fat diet mice, and increased uptake when vascular levels peaked. High-fat diet growth plates had more activated IGF-I receptors and fewer inhibitory binding proteins, suggesting increased IGF-I bioavailability in growth plates. These results, which parallel pediatric growth patterns, highlight the fundamental role of diet in the earliest stages of developing obesity-related skeletal complications and validate the utility of the model for future studies aimed at determining mechanisms of diet-enhanced bone lengthening.


2020 ◽  
Vol 21 (24) ◽  
pp. 9675
Author(s):  
Raquel Herrero-Labrador ◽  
Angel Trueba-Saiz ◽  
Laura Martinez-Rachadell ◽  
Mᵃ Estrella Fernandez de Sevilla ◽  
Jonathan A. Zegarra-Valdivia ◽  
...  

Obesity is a risk factor for Alzheimer’s disease (AD), but underlying mechanisms are not clear. We analyzed peripheral clearance of amyloid β (Aβ) in overweight mice because its systemic elimination may impact brain Aβ load, a major landmark of AD pathology. We also analyzed whether circulating insulin-like growth factor I (IGF-I) intervenes in the effects of overweight as this growth factor modulates brain Aβ clearance and is increased in the serum of overweight mice. Overweight mice showed increased Aβ accumulation by the liver, the major site of elimination of systemic Aβ, but unaltered brain Aβ levels. We also found that Aβ accumulation by hepatocytes is stimulated by IGF-I, and that mice with low serum IGF-I levels show reduced liver Aβ accumulation—ameliorated by IGF-I administration, and unchanged brain Aβ levels. In the brain, IGF-I favored the association of its receptor (IGF-IR) with the Aβ precursor protein (APP), and at the same time, stimulated non-amyloidogenic processing of APP in astrocytes, as indicated by an increased sAPPα/sAPPβ ratio after IGF-I treatment. Since serum IGF-I enters into the brain in an activity-dependent manner, we analyzed in overweight mice the effect of brain activation by environmental enrichment (EE) on brain IGF-IR phosphorylation and its association to APP, as a readout of IGF-I activity. After EE, significantly reduced brain IGF-IR phosphorylation and APP/IGF-IR association were found in overweight mice as compared to lean controls. Collectively, these results indicate that a high-fat diet influences peripheral clearance of Aβ without affecting brain Aβ load. Increased serum IGF-I likely contributes to enhanced peripheral Aβ clearance in overweight mice, without affecting brain Aβ load probably because its brain entrance is reduced.


2007 ◽  
Vol 103 (5) ◽  
pp. 1764-1771 ◽  
Author(s):  
Sunmin Park ◽  
Sang Mee Hong ◽  
Ji Eun Lee ◽  
So Ra Sung

In this study, we investigated the effects of a high-fat diet and exercise on pancreatic β-cell function and mass and its molecular mechanism in 90% pancreatectomized male rats. The pancreatectomized diabetic rats were given control diets (20% energy) or a high-fat (HF) diet (45% energy) for 12 wk. Half of each group was given regular exercise on an uphill treadmill at 20 m/min for 30 min 5 days/wk. HF diet lowered first-phase insulin secretion with glucose loading, whereas exercise training reversed this decrease. However, second-phase insulin secretion did not differ among the groups. Exercise increased pancreatic β-cell mass. This resulted from stimulated β-cell proliferation and reduced apoptosis, which is associated with potentiated insulin or IGF-I signaling through insulin receptor substrate-2 (IRS2) induction. Although the HF diet resulted in decreased proliferation and accelerated apoptosis by weakened insulin and IGF-I signaling from reduction of IRS2 protein, β-cell mass was maintained in HF rats just as much as in control rats via increased individual β-cell size and neogenesis from precursor cells. Consistent with the results of β-cell proliferation, pancreas duodenal homeobox-1 expression increased in the islets of rats in the exercise groups, and it was reduced the most in rats fed the HF diet. In conclusion, exercise combined with a moderate fat diet is a good way to maximize β-cell function and mass through IRS2 induction to alleviate the diabetic condition. This study suggests that dietary fat contents and exercise modulate β-cell function and mass to overcome insulin resistance in two different pathways.


2020 ◽  
Vol 90 (3-4) ◽  
pp. 221-227 ◽  
Author(s):  
Onur Atakisi ◽  
Kezban Yildiz Dalginli ◽  
Canan Gulmez ◽  
Ruya Kaya ◽  
Ozkan Ozden ◽  
...  

Abstract. The aim of this study was to investigate the effects of boric acid (BA) and borax (BX) on live weight and obesity associated molecules including leptin, L-carnitine, insulin-like growth factor 1 (IGF-I), and heat shock proteins 70 (HSP70) in rats fed with high-fat diet. A total of 60 rats were equally allocated as ND (normal diet), HF (high-fat diet), HF+BA, HF+BX, ND+BX, ND+BA. Body weight increases in HF+BA (85 g) and HF+BX (86 g) were significantly lower (p<0.05) compared to HF group (126 g). Boron treatment decreased serum L-carnitine level in high-fat diet (HF+BA 11.12 mg/L, HF+BX 10.51 mg/L, p<0.05) compared to HF group (15.57 mg/L), while no change was observed in groups ND+BA (7.55 mg/L) and ND+BX (7.57 mg/L) compared to group ND (8.29 mg/L). Neither BA nor BX supplementation in ND and HF groups altered the serum levels of HSP70 and leptin. BA and BX supplementation in rats fed HF resulted in a significant reduction in live weight. Boron compounds altered L-carnitine and IGF-1 levels in rats. These results indicate that boron compounds are beneficial in the treatment of obesity as well as in the prevention of high-fat diet-induced weight increase. Alterations in serum L-carnitine and IGF-1 levels in boron treated rats also indicate possible role of boron compounds in energy metabolism in response to high fat diet.


2012 ◽  
Vol 6 (1) ◽  
pp. 209-215
Author(s):  
Jin Ah Min ◽  
Sok Park ◽  
Ki-Woon Sung ◽  
Chang Hun Chae ◽  
Ji Youn Kim ◽  
...  

2015 ◽  
Vol 308 (7) ◽  
pp. E545-E553 ◽  
Author(s):  
Adam B. Salmon ◽  
Chad Lerner ◽  
Yuji Ikeno ◽  
Susan M. Motch Perrine ◽  
Roger McCarter ◽  
...  

The extension of lifespan due to reduced insulin-like growth factor 1 (IGF-I) signaling in mice has been proposed to be mediated through alterations in metabolism. Previously, we showed that mice homozygous for an insertion in the Igf1 allele have reduced levels of IGF-I, are smaller, and have an extension of maximum lifespan. Here, we tested whether this specific reduction of IGF-I alters glucose metabolism both on normal rodent chow and in response to high-fat feeding. We found that female IGF-I-deficient mice were lean on a standard rodent diet but paradoxically displayed an insulin-resistant phenotype. However, these mice gained significantly less weight than normal controls when placed on a high-fat diet. In control animals, insulin response was significantly impaired by high-fat feeding, whereas IGF-I-deficient mice showed a much smaller shift in insulin response after high-fat feeding. Gluconeogenesis was also elevated in the IGF-I-deficient mice relative to controls on both normal and high-fat diet. An analysis of metabolism and respiratory quotient over 24 h indicated that the IGF-I-deficient mice preferentially utilized fatty acids as an energy source when placed on a high-fat diet. These results indicate that reduction in the circulating and tissue IGF-I levels can produce a metabolic phenotype in female mice that increases peripheral insulin resistance but renders animals resistant to the deleterious effects of high-fat feeding.


2019 ◽  
Vol 89 (1-2) ◽  
pp. 45-54
Author(s):  
Akemi Suzuki ◽  
André Manoel Correia-Santos ◽  
Gabriela Câmara Vicente ◽  
Luiz Guillermo Coca Velarde ◽  
Gilson Teles Boaventura

Abstract. Objective: This study aimed to evaluate the effect of maternal consumption of flaxseed flour and oil on serum concentrations of glucose, insulin, and thyroid hormones of the adult female offspring of diabetic rats. Methods: Wistar rats were induced to diabetes by a high-fat diet (60%) and streptozotocin (35 mg/kg). Rats were mated and once pregnancy was confirmed, were divided into the following groups: Control Group (CG): casein-based diet; High-fat Group (HG): high-fat diet (49%); High-fat Flaxseed Group (HFG): high-fat diet supplemented with 25% flaxseed flour; High-fat Flaxseed Oil group (HOG): high-fat diet, where soya oil was replaced with flaxseed oil. After weaning, female pups (n = 6) from each group were separated, received a commercial rat diet and were sacrificed after 180 days. Serum insulin concentrations were determined by ELISA, the levels of triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) were determined by chemiluminescence. Results: There was a significant reduction in body weight at weaning in HG (−31%), HFG (−33%) and HOG (44%) compared to CG (p = 0.002), which became similar by the end of 180 days. Blood glucose levels were reduced in HFG (−10%, p = 0.044) when compared to CG, and there was no significant difference between groups in relation to insulin, T3, T4, and TSH after 180 days. Conclusions: Maternal severe hyperglycemia during pregnancy and lactation resulted in a microsomal offspring. Maternal consumption of flaxseed reduces blood glucose levels in adult offspring without significant effects on insulin levels and thyroid hormones.


Obesity ◽  
2012 ◽  
Author(s):  
Gong-Rak Lee ◽  
Mi Kyung Shin ◽  
Dong-Joon Yoon ◽  
Ah-Ram Kim ◽  
Rina Yu ◽  
...  

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