Medical Bulletin 27/ March/ 2024

Estrogen potentially contributes to nicotine addiction among women, finds study

A newly discovered feedback loop involving estrogen may explain why women might become dependent on nicotine more quickly and with less nicotine exposure than men.

Presented at the Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology, the study revealed that the discovery could lead to new treatments for women who are having trouble quitting nicotine-containing products such as cigarettes.

“Studies show that women have a higher propensity to develop addiction to nicotine than men and are less successful at quitting. Our work aims to understand what makes women more susceptible to nicotine use disorder to reduce the gender disparity in treating nicotine addiction,” said Sally Pauss, doctoral student at the University of Kentucky College of Medicine in Lexington.

For the new study, the researchers used large sequencing datasets of estrogen-induced genes to identify genes that are expressed in the brain and exhibit a hormone function. They found just one class of genes that met these criteria: those coding for olfactomedins. They then performed a series of studies with human uterine cells and rats to better understand the interactions between olfactomedins, estrogen and nicotine.

The researchers found that the sex hormone estrogen induces the expression of olfactomedins, proteins that are suppressed by nicotine in key areas of the brain involved in reward and addiction.

The results revealed that estrogen activation of olfactomedins — which is suppressed when nicotine is present — might serve as a feedback loop for driving nicotine addiction processes by activating areas of the brain’s reward circuitry such as the nucleus accumbens.

The findings suggested that estrogen–nicotine–olfactomedin interactions could be targeted with therapies to help control nicotine consumption.

“Our research has the potential to better the lives and health of women struggling with substance use. If we can confirm that estrogen drives nicotine seeking and consumption through olfactomedins, we can design drugs that might block that effect by targeting the altered pathways. These drugs would hopefully make it easier for women to quit nicotine.” said Pauss

Reference: Sally Pauss, University of Kentucky; Zachary Kipp, University of Kentucky; Cassandra Gipson-Reichardt, University of Kentucky; Terry Hinds, University of Kentucky; AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY; Meeting: Discover BMB

Aspirin may help reduce liver fat, reveals study

The most common chronic liver disease—called metabolic dysfunction–associated steatotic liver disease (MASLD)—is characterised by an increased buildup of fat in the liver due to factors such as obesity and type 2 diabetes.

A recent clinical trial published in the journal JAMA and conducted by investigators from Massachusetts General Hospital revealed that daily aspirin can significantly reduce liver fat content.

“Since MASLD is estimated to affect up to a third of adults, aspirin represents an attractive potential low-cost option to prevent progression to cirrhosis or liver cancer, the most feared complications of MASLD,” said senior author Andrew T. Chan, MD, MPH, a gastroenterologist and chief of the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital.

In the study, Chan and his colleagues tested aspirin’s potential because the drug reduces inflammation and affects fat metabolism. In their phase 2 trial, 80 adults with MASLD were randomised to receive daily low-dose aspirin (81 mg) or placebo for six months. At the end of the trial, the average change in liver fat content was -6.6% with aspirin versus +3.6% with placebo, indicating that low-dose aspirin reduced the average liver fat content by 10.2% compared with placebo. Low-dose aspirin was found to be safe and well-tolerated.

“Aspirin also improved various markers of liver health. Multiple non-invasive blood and imaging-based tests for liver fat, inflammation, and fibrosis all showed a similar direction of benefit that favoured aspirin treatment. Together, these data support the potential for aspirin to provide benefits for patients with MASLD” said lead author and Principal Investigator Tracey G. Simon, MD, MPH, a hepatologist in the Division of Gastroenterology at Massachusetts General Hospital.

Reference: Tracey G. Simon, MD, MPH; Robert M. Wilechansky, MD; Stefania Stoyanova,; et al; Journal: JAMA Network; DOI: 10.1001/jama.2024.1215

Does consumption of reused deep-fried oil lead to neurodegeneration?

A new study presented at the Discover BMB revealed higher levels of neurodegeneration in rats that consumed reused deep-fried cooking oils and their offspring compared to rats on a normal diet.

Deep frying, which involves completely submerging food in hot oil, is a common method of food preparation around the world. Deep frying food not only adds calories; reusing the same oil for frying, a common practice removes many of the oil’s natural antioxidants and health benefits. Oil that is reused also can contain harmful components such as acrylamide, trans fat, peroxides and polar compounds.

“Deep-frying at high temperatures has been linked with several metabolic disorders, but there have been no long-term investigations on the influence of deep-fried oil consumption and its detrimental effects on health. To our knowledge we are the first to report long-term deep-fried oil supplementation increases neurodegeneration in the first-generation offspring,” said Kathiresan Shanmugam, an associate professor from Central University of Tamil Nadu in Thiruvarur who led the research team.

To explore the long-term effects of reused deep-fried frying oil, the researchers divided female rats into five groups that each received either standard chow alone or standard chow with 0.1 ml per day of unheated sesame oil, unheated sunflower oil, reheated sesame oil or reheated sunflower oil for 30 days. The reheated oils simulated reused frying oil.

Compared with the other groups, the rats that consumed reheated sesame or sunflower oil showed increased oxidative stress and inflammation in the liver. These rats also showed significant damage in the colon that brought on changes in endotoxins and lipopolysaccharides — toxins released from certain bacteria.

“As a result, liver lipid metabolism was significantly altered, and the transport of the important brain omega-3 fatty acid DHA was decreased. This, in turn, resulted in neurodegeneration, which was seen in the brain histology of the rats consuming the reheated oil as well as their offspring,” said Shanmugam.

Although more studies are needed, the researchers suggested that supplementation with omega-3 fatty acids and nutraceuticals such as curcumin and oryzanol might be helpful in reducing liver inflammation and neurodegeneration.

Reference: Sugasini Dhavamani, University of Illinois at Chicago, Jeyakumar Balakrishnan, Vinayaka Mission's Medical College and Hospital, Kathiresan Shanmugam, Central University of Tamilnadu; AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY; MEETING: Discover BMB