Genetic Background (C57BL/6J Versus FVB/N) Strongly Influences the Severity of Diabetes and Insulin Resistance in ob/ob Mice

Haluzı́k, Martin; Colombo, Carlo; Гаврилова, Оксана; Chua, Streamson C.; Wolf, Nicole J.; Chen, Min; Stannard, Bethel; Dietz, K; Roith, Derek Le; Reitman, Marc L.

doi:10.1210/en.2004-0219

Cited by 169 publications

(150 citation statements)

References 37 publications

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“…Moreover, a number of genetic modifications leading to diabetes show diminished or no effect in this strain. 77 Mouse strains differ in their vascular response to diabetes and hyperlipidemia. Kunjathoor et al 78 assessed atherosclerosis in several strains of STZ-treated and cholic acidcontaining (Paigen) diet fed mice.…”

Section: Do Mouse Models Reproduce the Relationship Between Diabetes mentioning

confidence: 99%

Diabetic Vascular Disease

Goldberg

Dansky

2006

ATVB

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Abstract-It is well known that humans with diabetes have more atherosclerosis and its complications. The causes of this relationship are, however, unclear. Although recent data show that improved glycemic control reduces arterial disease in type 1 diabetes, other studies have shown that subjects with "prediabetes" have more cardiovascular disease before the development of hyperglycemia. Thus, either hyperglycemia and/or lack of insulin actions are toxic to arteries, or metabolic derangements exclusive of hyperglycemia are atherogenic. For Ͼ50 years animal models of diabetes and atherosclerosis have been used to uncover potential mechanisms underlying diabetes associated cardiovascular disease. Surprisingly, diabetes alone increases vascular disease in only a few select animal models. Increased atherosclerosis has been found in several animals and lines of genetically modified mice; however, diabetes often also leads to greater hyperlipidemia. This makes it difficult to separate the toxic effects of insulin lack and/or hyperglycemia from those caused by the lipids. These studies are reviewed, as well as more recent investigations using new methods to create diabetic-atherosclerotic models.

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Section: Do Mouse Models Reproduce the Relationship Between Diabetes mentioning

confidence: 99%

Diabetic Vascular Disease

Goldberg

Dansky

2006

ATVB

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“…Highly augmented serum levels of triglycerides, free fatty acids, oxidised lipoproteins, insulin and glucose are the pathophysiological consequences in obese persons. 10 In ob/ob mice, increase of these serum factors is associated with mild diabetes in the ob/ob mouse 11,12 and with excessively accumulated lipid droplets in cells of follicles and of the ovarian cortex. 8,13 The striking intraovarian lipogenesis is probably responsible for mitochondrial dysfunction with the augmented release of reactive oxygen species (ROS) leading to oxidative stress and cellular damage.…”

Section: Introductionmentioning

confidence: 99%

Leptin-deficient (ob/ob) mouse ovaries show fatty degeneration, enhanced apoptosis and decreased expression of steroidogenic acute regulatory enzyme

et al. 2011

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OBJECTIVE: Leptin-deficient (ob/ob) mice are obese and infertile. Dysfunctions of the ovaries are preferentially related to leptin-deficiency. DESIGN: Morphological and molecular biological obesity-dependent changes in ob/ob ovaries. SUBJECTS: Ovaries were obtained from three-month-old mice either homozygote (ob/ob) and heterozygote (ob/ þ ) or wild-type (C57BL6, WT) for the investigation by light and electron microscopy, as well as for western blot analysis of lectin-like oxidised low density lipoprotein receptor (LOX-1), Toll-like receptor 4 (TLR4), CD36, cleaved caspase-3, microtubule-associated protein light chain 3 (LC3), and the steroidogenic acute regulatory protein (StAR). RESULTS: Compared with control ovaries with corpora lutea, ob/ob ovaries lacked corpora lutea, follicular atresia was at a higher rate; lipid droplets accumulated in follicle cells and in the oocyte with damaged mitochondria; the basement membrane of follicles was thickened. LOX-1 and CD36 expressions were comparable for all three groups. Ob/ob ovaries showed significantly higher levels of TLR4 and cleaved caspase-3 than the ones from the control groups. The high LC3-II/I ratio in the WT and ob/ þ ovaries was related to the presence of corpora lutea. The StAR protein was lower in the ob/ob ovaries signifying reduced steroidogenesis. CONCLUSIONS: Excessive lipid storage causes disorders of ovarian function in ob/ob mice. The local lipid overload leads to advanced follicular atresia with apoptosis and defect steroidogenesis. We suggest that the changes in lipid metabolism lead to increased oxidative stress and thereby, they are an important reason of anovulation and infertility.

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“…Adiponectin (Acrp30) is synthesized and secreted exclusively by adipocytes (16), and many studies have shown that high levels of adiponectin are associated with insulin sensitivity whereas low levels are found in insulin resistance (8,9,17). Furthermore, direct experiments have demonstrated that adiponectin can mediate insulin-sensitizing effects, most likely by activating AMP-activated protein kinase (AMPK).…”

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confidence: 99%