Fetal nicotine exposure blamed for later obesity
By Adela Talbot
January 30, 2014
If your mother smoked cigarettes during pregnancy, you are more likely to battle the bulge later in life. But it’s not enough to blame cigarettes – nicotine is the culprit, according to new research at Western.
“Thirty prospective studies have now demonstrated that if you are born to a mother who smoked, you have a 40 per cent increase in the risk of developing obesity,” said Daniel Hardy, a professor in the Department of Obstetrics and Gynecology, with a cross-appointment in the Department of Physiology and Pharmacology, at Western’s Schulich School of Medicine & Dentistry.
Today, pregnant women are encouraged to quit smoking during pregnancy. To aid in that, they are given Nicotine Replacement Therapy (NRT) in the form of gum, transdermal patches, nasal spray or lozenges. Hardy’s study, recently published in Toxicology and Applied Pharmacology, found nicotine, regardless of the source, was to blame for an increased likelihood of obesity.
Hardy, who led the study, partnered with Alison Holloway at McMaster University and Noelle Ma, a postgraduate student working in his lab. The team administered the equivalent of 1 mg of nicotine per 1 kg of body weight, per day to pregnant lab rats. This equals the amount of nicotine a moderate smoker would take in each day.
“We stopped (administering the nicotine) after birth and we followed up with these animals six months later. Remarkably, the levels of triglycerides, the hallmarks of obesity, was elevated in the animals only exposed to nicotine in pregnancy, compared to the control group,” Hardy explained.
“We went on then to look at why they make more triglycerides. The liver is a major source of triglyceride synthesis and we found the livers (of the test group) had elevated enzymes that make triglycerides. So, there’s a true link now between nicotine exposure alone and increased triglycerides,” he continued.
Triglycerides are a type of fat found in your blood. When you eat, your body converts any calories it doesn't need to use right away into triglycerides. The triglycerides are stored in your fat cells. Later, hormones release triglycerides for energy between meals. If you regularly eat more calories than you burn, particularly ‘easy’ calories like carbohydrates and fats, you may have high triglycerides.
“This tells you nicotine is having some direct effect on the liver that catches up to you six months later if you’re a rat offspring,” Hardy continued. “The idea it’s nicotine alone is quite fascinating, because obviously, we now know NRT is widely accepted, short-term, in pregnancy.”
Obstetricians prescribe NRT to smoking pregnant women in doses that average around 10 mg per day, significantly more than the average smoker would take in and more than Hardy administered in the lab.
“Our study shows it’s nicotine alone that’s causing the increase in triglycerides later on. It raises some interesting questions like whether or not we should continue the current practice, the dose or the timing of NRT during pregnancy in humans,” he said.
In the future, Hardy and his team have proposed a larger human study looking at NRT in pregnancy and its relation to childhood obesity.
“We know we can’t necessarily avoid NRT. It’s the lesser of two evils compared to smoking. But can we intervene in early life, knowing that these offspring were exposed to nicotine? Can we intervene to stop them from developing high triglycerides and obesity?”
Looking at the animal model, Hardy said offspring of mothers exposed to nicotine had low levels of folic acid, also known as folate.
“So, we want to know, in our animal models, if we supplement with folic acid, will we reduce triglycerides? Other animal studies have demonstrated in newborns that folic acid decreases triglycerides, so if we do it in our animal model, will that be a rescue mechanism?” he continued.
“It’s not just about saying nicotine is bad in pregnancy, but more importantly, now that we know, or can identify that you were exposed to nicotine, how can we intervene and keep an eye on these children long-term?”
Department of Obstetrics and Gynecology, with a cross appointment in the Department of Physiology and Pharmacology,
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