High-Fat Diet Is Associated with Obesity-Mediated Insulin Resistance and β-Cell Dysfunction in Mexican Americans

Black, Maureen M.; Watanabe, Richard M.; Trigo, Enrique; Takayanagi, Miwa; Lawrence, Jean M.; Buchanan, Thomas A.; Xiang, Anny H.

doi:10.3945/jn.112.170449

Cited by 43 publications

(38 citation statements)

References 30 publications

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“…In general, a high-fat diet is associated with obesity-mediated insulin resistance [45] and with elevated total serum cholesterol and triglyceride levels and inhibiting the absorption of triglycerides have an important role in weight loss [46]. In this study, BP diet tended to decrease the serum level of total cholesterol and triglyceride in comparison with rat given the high-fat control fat.…”

Section: Discussionmentioning

confidence: 58%

Blueberry Peel Extracts Inhibit Adipogenesis in 3T3-L1 Cells and Reduce High-Fat Diet-Induced Obesity

et al. 2013

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This study examined the anti-obesity effect and mechanism of action of blueberry peel extracts (BPE) in 3T3-L1 cells and high-fat diet (HFD)-induced obese rats. The levels of lipid accumulation were measured, along with the changes in the expression of genes and proteins associated with adipocyte differentiation in 3T3-L1 cells. Evidenced by Oil-red O staining and triglyceride assay, BPE dose-dependently inhibited lipid accumulation at concentrations of 0, 50, and 200 µg/ml. BPE decreased the expression of the key adipocyte differentiation regulator C/EBPβ, as well as the C/EBPα and PPARγ genes, during the differentiation of preadipocytes into adipocytes. Moreover, BPE down-regulated adipocyte-specific genes such as aP2 and FAS compared with control adipocytes. The specific mechanism mediating the effects of BP revealed that insulin-stimulated phosphorylation of Akt was strongly decreased, and its downstream substrate, phospho-GSK3β, was downregulated by BPE treatment in 3T3-L1 cells. Together, these data indicated that BP exerted anti-adipogenic activity by inhibiting the expression of PPARγ and C/EBPβ and the Akt signaling pathway in 3T3-L1 adipocytes. Next, we investigated whether BP extracts attenuated HFD-induced obesity in rats. Oral administration of BPE reduced HFD-induced body weight gain significantly without affecting food intake. The epididymal or perirenal adipose tissue weights were lower in rats on an HFD plus BPE compared with the tissue weights of HFD-induced obese rats. Total cholesterol and triglyceride levels in the rats fed BPE were modestly reduced, and the HDL-cholesterol level was significantly increased in HFD plus BP-fed rats compared with those of HFD-fed rats. Taken together, these results demonstrated an inhibitory effect of BP on adipogenesis through the down-regulation of C/EBPβ, C/EBPα, and PPARγ and the reduction of the phospho-Akt adipogenic factor in 3T3-L1 cells. Moreover, BPE reduced body weight gain and inhibited fat accumulation in an HFD-induced animal model of obesity.

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Section: Discussionmentioning

confidence: 58%

Blueberry Peel Extracts Inhibit Adipogenesis in 3T3-L1 Cells and Reduce High-Fat Diet-Induced Obesity

et al. 2013

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“…Mice fed chronic HFDs revealed beta cell dysfunction, impaired glucose‐stimulated insulin secretion and glucose intolerance as a consequence of insulin resistance . HFDs may contribute to increased adiposity and the associated insulin resistance and beta cell dysfunction prior to overt diabetes . These studies link HFDs to obesity, insulin resistance, beta cell compensation, and beta cell dysfunction.…”

Section: High Fat (Hf) Diets Obesity Insulin Resistance and Beta Cmentioning

confidence: 88%

High fat programming of beta cell compensation, exhaustion, death and dysfunction

Cerf

2014

Pediatr Diabetes

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Programming refers to events during critical developmental windows that shape progeny health outcomes. Fetal programming refers to the effects of intrauterine (in utero) events. Lactational programming refers to the effects of events during suckling (weaning). Developmental programming refers to the effects of events during both fetal and lactational life. Postnatal programming refers to the effects of events either from birth (lactational life) to adolescence or from weaning (end of lactation) to adolescence. Islets are most plastic during the early life course; hence programming during fetal and lactational life is most potent. High fat (HF) programming is the maintenance on a HF diet (HFD) during critical developmental life stages that alters progeny metabolism and physiology. HF programming induces variable diabetogenic phenotypes dependent on the timing and duration of the dietary insult. Maternal obesity reinforces HF programming effects in progeny. HF programming, through acute hyperglycemia, initiates beta cell compensation. However, HF programming eventually leads to chronic hyperglycemia that triggers beta cell exhaustion, death and dysfunction. In HF programming, beta cell dysfunction often co-presents with insulin resistance. Balanced, healthy nutrition during developmental windows is critical for preserving beta cell structure and function. Thus early positive nutritional interventions that coincide with the development of beta cells may reduce the overwhelming burden of diabetes and metabolic disease.

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“…Both lean and obese women with PCOS have peripheral IR and hyperinsulinemia [26]. The IR associated with obesity or habitual consumption of fatty diets has been linked to increased cellular levels of stored TG and fatty acid derivatives [27,28]. Several studies have implicated that increased expression of Hsp70 is involved in the pathogenesis of insulin-resistant disorders such as the metabolic syndrome [12] and T2DM [18] in the general population.…”

Section: Discussionmentioning

confidence: 99%

Serum Heat Shock Protein 70 Concentration in Relation to Polycystic Ovary Syndrome in a Non-Obese Chinese Population

Gao

Meng

et al. 2013

PLoS ONE

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BackgroundPolycystic ovary syndrome (PCOS) represents the most common cause of anovulatory infertility and affects 6-15% of women of reproductive age. However, the underlying etiology is still poorly understood. In this study, we attempted to examine the association between circulating heat shock protein 70 (Hsp70) concentrations and PCOS in a non-obese Chinese population.Methods and ResultsHuman peripheral blood from 52 patients with PCOS and 57 healthy controls, matched for age and BMI, were analyzed. Women with PCOS were found to have significantly higher fasting insulin (FI) levels, as well as Insulin resistance index (HOMA-IR) (P < 0.05). Identically, markers of oxidative stress (malondialdehyde (MDA), 8-Hydroxy-desoxyguanosine (8-OHdG), Nitric oxide (NO)) and inflammation (tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP)) were markedly increased when compared to controls (P < 0.05). Elevated serum Hsp70 was positively correlated with IR, oxidative stress and inflammation in PCOS, even after adjustment for age, BMI and gynecologic inflammation (GI). The receiver-operating characteristic curve (ROC) analysis yielded notably different discriminative value for PCOS, with or without an addition of Hsp70 (areas under the curves were 0.884 (95% CI 0.822-0.946) vs. 0.822 (95% CI 0.744-0.900); P for difference = 0.015).Conclusions and SignificanceIncreased serum Hsp70 levels are associated with the combination of IR, oxidative stress and low-grade chronic inflammation in PCOS individuals, which provides supportive evidence that Hsp70 plays a key role in the pathogenesis of PCOS. More consequent studies were warranted to confirm the clinical utility of circulating Hsp70, especially in diagnosis and prognosis of PCOS and its long-term health cost.

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High-Fat Diet Is Associated with Obesity-Mediated Insulin Resistance and β-Cell Dysfunction in Mexican Americans

Cited by 43 publications

References 30 publications

Blueberry Peel Extracts Inhibit Adipogenesis in 3T3-L1 Cells and Reduce High-Fat Diet-Induced Obesity

Blueberry Peel Extracts Inhibit Adipogenesis in 3T3-L1 Cells and Reduce High-Fat Diet-Induced Obesity

High fat programming of beta cell compensation, exhaustion, death and dysfunction

Serum Heat Shock Protein 70 Concentration in Relation to Polycystic Ovary Syndrome in a Non-Obese Chinese Population

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