Molecular mechanisms of cancer development in obesity

Khandekar, Melin J.; Cohen, Paul; Spiegelman, Bruce M.

doi:10.1038/nrc3174

Cited by 767 publications

(678 citation statements)

References 164 publications

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“…Epidemiological studies link obesity with several types of cancers. 6,34 However, the biological mechanisms underlying the link between obesity and cancer and the possible role of p53 in this pathway are still poorly understood. Abrogation of p53 function, by its deficiency or mutation, apparently results in aberrant differentiation, which may give rise to transformed cells.…”

Section: Discussionmentioning

confidence: 99%

“…4 Disruption of normal metabolic homeostasis in obesity leads to the development of several pathological conditions such as insulin resistance, type 2 diabetes and increased risk of development of a variety of cancers. 2,5,6 Results from several studies indicated that there is an inverse correlation between BAT activity and obesity. [7][8][9] Thus, increasing brown adipose tissue mass or activity could be a useful approach to limit obesity and its associated disease states.…”

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confidence: 99%

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p53 is required for brown adipogenic differentiation and has a protective role against diet-induced obesity

et al. 2013

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Proper regulation of white and brown adipogenic differentiation is important for maintaining an organism's metabolic profile in a homeostatic state. The recent observations showing that the p53 tumor suppressor plays a role in metabolism raise the question of whether it is involved in the regulation of white and brown adipocyte differentiation. By using several in vitro models, representing various stages of white adipocyte differentiation, we found that p53 exerts a suppressive effect on white adipocyte differentiation in both mouse and human cells. Moreover, our in vivo analysis indicated that p53 is implicated in protection against diet-induced obesity. In striking contrast, our data shows that p53 exerts a positive regulatory effect on brown adipocyte differentiation. Abrogation of p53 function in skeletal muscle committed cells reduced their capacity to differentiate into brown adipocytes and histological analysis of brown adipose tissue revealed an impaired morphology in both embryonic and adult p53-null mice. Thus, depending on the specific adipogenic differentiation program, p53 may exert a positive or a negative effect. This cell type dependent regulation reflects an additional modality of p53 in maintaining a homeostatic state, not only in the cell, but also in the organism at large.

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Section: Discussionmentioning

confidence: 99%

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p53 is required for brown adipogenic differentiation and has a protective role against diet-induced obesity

et al. 2013

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“…Excess adipose tissue leads to metabolic changes such as reduced high-density lipoprotein cholesterol, elevated triglycerides, hypertension, and insulin resistance (Khandekar et al, 2011). Obesityinduced esophageal reflux, hypertension, insulin resistance, and hormone alternations could contribute to an increased risk in esophageal, kidney, colorectal, and breast cancers, respectively (Wang and Dubois, 2012).…”

Section: Allium Cepa Leffects On Proliferation Of Cancer Cells and Amentioning

confidence: 99%

Inhibitory Effects of Onion (Allium cepa L.) Extract on Proliferation of Cancer Cells and Adipocytes via Inhibiting Fatty Acid Synthase

Wang¹,

Tian²,

Ma³

2012

Asian Pacific Journal of Cancer Prevention

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Onions (Allium cepa L.) are widely used in the food industry for its nutritional and aromatic properties. Our studies showed that ethyl acetate extract of onion (EEO) had potent inhibitory effects on animal fatty acid synthase (FAS), and could induce apoptosis in FAS over-expressing human breast cancer MDA-MB-231 cells. Furthermore, this apoptosis was accompanied by reduction of intracellular FAS activity and could be rescued by 25 mM or 50 mM exogenous palmitic acids, the final product of FAS catalyzed synthesis. These results suggest that the apoptosis induced by EEO occurs via inhibition of FAS. We also found that EEO could suppress lipid accumulation during the differentiation of 3T3-L1 adipocytes, which was also related to its inhibition of intracellular FAS activity. Since obesity is closely related to breast cancer and obese patients are at elevated risk of developing various cancers, these findings suggested that onion might be useful for preventing obesity-related malignancy.

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“…It has been reported that increase in visceral adipose tissue above the normal level (represented by waist circumference >102 cm in men and > 88 cm in women) is a risk factor in esophageal cancer and, to a lesser extent, colorectal cancer [54]. A strong association was reported between adipose tissue in the abdominal area (visceral fat) and increased levels of inflammatory markers leading to cancer initiation as a result of the imbalance in the counter-regulating hormones such as leptin and adiponectin [55]. Leptin and adiponectin were found to be inversely associated with body weight changes: those with higher body weights have higher levels of leptin, while those with lower body weight have higher adiponectin levels [56].…”

Section: Role Of Adipose Tissues In Cancer Developmentmentioning

confidence: 99%

Obesity and Cancer: What’s the Interconnection?

Faris¹

2015

AOWMC

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Obesity is one of the most prevalent nutritional diseases, associated with chronic morbidity and mortality. Persuasive evidence indicates a striking association between obesity and incidence of common neoplasms, such as those of the esophagus, endometrium, kidney and breast in post menopause women, prostate in men, in addition to colon, rectum and bladder. Such an association has been supported by clinical and laboratory experiments on humans and animals, respectively. The findings have revealed that obesity and increased body fatness, in general and visceral adiposity, in particular, increase the vulnerability to develop different cancers. Although the impact of obesity in cancer progression differs according to the type of cancer, all the obesity-related cancers are centered around body adiposity. This review highlights the different hormonal, biochemical and molecular changes that might be involved in obesity-related cancers. Increased serum insulin, insulin-like growth factor, steroids "sex hormones" and the disturbances in adiponectin and leptin hormones are included. Biochemical and metabolic changes that mediate obesity-related carcinogenesis involving elevated oxidative stress and inflammation levels in the body and the concomitant increment in circulatory proinflammatory cytokines are discussed.

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Molecular mechanisms of cancer development in obesity

Cited by 767 publications

References 164 publications

p53 is required for brown adipogenic differentiation and has a protective role against diet-induced obesity

p53 is required for brown adipogenic differentiation and has a protective role against diet-induced obesity

Inhibitory Effects of Onion (Allium cepa L.) Extract on Proliferation of Cancer Cells and Adipocytes via Inhibiting Fatty Acid Synthase

Obesity and Cancer: What’s the Interconnection?

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