02:54am Monday 06 July 2020

Moderating the effects of obesity on liver cancer progression

News Article ImageFat cells secrete a variety of hormones, some of which can have tumor growth-stimulating effects. However, scientists have dubbed adiponectin a “guardian angel” hormone because it appears to protect against the effects of obesity on metabolism and cardiovascular health.

Dipali Sharma, PhD, first author of the paper. Sharma is assistant professor of hematology and medical oncology at Emory University School of Medicine and Winship Cancer Institute.

The results, scheduled for publication in the November issue of the journal Hepatology, suggest that treatments that mimic or enhance adiponectin’s effects could enhance survival for obese individuals with liver cancer.

“Our study presents important clinical implications since hepatocellular carcinoma has the highest increased risk associated with obesity compared to other cancers such as prostate, kidney, colon, and stomach,” says senior author Neeraj Saxena, PhD, assistant professor of medicine (digestive diseases) at Emory University School of Medicine.

The first author of the paper is Dipali Sharma, PhD, assistant professor of hematology and medical oncology at Emory University School of Medicine and Winship Cancer Institute.

Hepatocellular carcinoma is one of the most common tumor types worldwide, but is relatively rare in the United States. The rate is increasing because of hepatitis C and obesity. Obesity is associated with increased risk and progression of a number of cancers including colon, prostate, breast, and liver cancers. Obese people have about a 1.5-fold increase in their risk of all types of cancer, but for liver cancer, obesity increases the risk 4.5-fold.

Obese populations tend to have higher circulating levels of the hormone leptin, but they may be resistant to some of its appetite-controlling effects. Weight loss tends to increase adiponectin, and low levels of adiponectin are found in patients with aggressive tumors.

One of the main roles of adiponectin is to counteract the effects of leptin. Adiponectin also regulates glucose levels and the breakdown of fatty acids. The levels of adiponectin can partially predict tumor growth, size and disease-free survival in human liver cancers, the authors found. In addition, they found that exposing liver cancer cells to adiponectin can reduce their ability to proliferate and invade other tissues, both in cell culture and in animal models.

“Taken together our results suggest an attractive molecular strategy: employing adiponectin analogues for potential therapy of metastatic hepatocellular carcinoma,” Saxena says.

Previous research by Sharma and Saxena has shown that adiponectin can also inhibit migration and invasion by breast cancer cells. (LINK)

Anti-diabetic drugs known as thiazolidinediones can increase adiponectin’s activity, but they have side effects on the heart that has led to their restriction by the FDA. The effects of injecting high levels of the hormone directly are unknown and need to be tested. Scientists are investigating other ways to increase a patient’s adiponectin, as wells as mutant forms of the leptin protein that may block leptin’s effects on cancer cells. Some natural compounds, such as those found in green tea, may be able to mimic the effects of adiponectin.

The research was supported by the National Cancer Institute and the National Institute of Diabetes and Digestive and Kidney Diseases.

Reference: D. Sharma et al. Adiponectin antagonizes the oncogenic actions of leptin in hepatocellular carcinogenesis. Page #’s. Hepatology (Nov 2010).


The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service. Its components include the Emory University School of Medicine, Nell Hodgson Woodruff School of Nursing, and Rollins School of Public Health; Yerkes National Primate Research Center; Winship Cancer Institute of Emory University; and Emory Healthcare, the largest, most comprehensive health system in Georgia. Emory Healthcare includes: The Emory Clinic, Emory-Children’s Center, Emory University Hospital, Emory University Hospital Midtown, Wesley Woods Center, and Emory University Orthopaedics & Spine Hospital.  The Woodruff Health Sciences Center has a $2.5 billion budget, 17,600 employees, 2,500 full-time and 1,500 affiliated faculty, 4,700 students and trainees, and a $5.7 billion economic impact on metro Atlanta.


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