Scientists “may have uncovered a key reason why obese people have a raised risk of health complications such as type 2 diabetes”, BBC News has said. According to the news service, the link is due to ‘pigment epithelium-derived factor’ (PEDF), a protein released from fat cells.

The results of the study suggest that insulin resistance in obesity, and hence the increased likelihood of diabetes, may be partly caused by PEDF. ‘Obese’ mice, who were resistant to insulin and had elevated blood glucose levels, also had elevated levels of PEDF. When PEDF was injected into ‘lean’ mice, it also reduced their sensitivity to the effects of insulin, as might be seen in type 2 diabetes.

This is worthy research, which has attempted to understand the possible biological mechanisms that link obesity and the increased risk of diabetes. However, as this is only an animal study, the situation may differ in humans. More research is needed to clarify whether this might have future treatment implications, such as techniques to block the action of PEDF and increase insulin sensitivity. For the general population, a healthy diet and lifestyle with regular exercise remains the best way to avoid obesity and the risk of complications such as type 2 diabetes.

 

Where did the story come from?

The research was carried out by Seamus Crowe and colleagues of Monash University, Australia and other institutions in Australia and the US. The studies were supported by research grants from
the National Health and Medical Research Council of Australia and the Diabetes Australia Research Trust. Individual researchers also received scholarships and fellowship support. The study was published in Cell, the peer-reviewed scientific journal.

 

What kind of scientific study was this?

This was an experimental study in mice, looking at the link between obesity and glucose intolerance. The researchers say that although obesity is identified as a major risk factor for glucose intolerance and diabetes in humans, the factors linking these disorders are not clearly understood. In this paper, researchers attempted to examine the possible underlying mechanism.

Previous research is said to have focused on trying to identify proteins that are secreted from fat cells. Screening has identified one of the most abundant of these proteins to be ‘pigment epithelium-derived factor’ (PEDF or SerpinF1), an enzyme inhibitor believed to have a role in the regulation of metabolism. This mouse study aimed to investigate the role that PEDF plays in increasing resistance to insulin, and hence intolerance of glucose, in fat mice.

For 12 weeks the researchers fed one group of mice on a low-fat diet (4% fat) of mouse chow, while feeding another on a high-fat diet (60% fat). They then compared the mice’s body mass and levels of fatty tissue, in addition to levels of PEDF in the blood.

To see how PEDF regulates the sensitivity of the muscle cells to insulin, the researchers injected PEDF into muscle cells taken from the low-fat mice, observing how this affected glucose uptake by the muscle cells.

They further tested PEDF’s action by injecting the low-fat mice with PEDF, then stimulated them with high levels of insulin but aimed to keep their glucose levels stable. They tried to achieve this by giving the mice extra glucose when their levels began to fall.

 

What were the results of the study?

Mice fed on the high-fat diet had increased body mass and fatty tissue compared to those on the low-fat diet. The high-fat mice also had comparatively increased blood glucose levels and elevated insulin, suggesting that they were resistant to insulin.

The blood concentration of PEDF in the high-fat mice was also increased 3.2-fold compared to the concentration in the low-fat mice, with later tissue analysis revealing that their fat cells were secreting more PEDF than the lean mice but their muscle and liver cells were not secreting excess amounts.

When looking to see how injected PEDF affected insulin sensitivity in the extracted muscle cells, the researchers found that it reduced the insulin-induced uptake of glucose, i.e. PEDF decreased their sensitivity to insulin.

In the subsequent test where they injected the low-fat mice with PEDF while trying to maintain high insulin/stable glucose levels, they found that, compared to mice who were not injected, those who were given PEDF needed to be given less glucose to keep their glucose levels stable during insulin stimulation. This indicated that their bodies had greater resistance to insulin when injected with PEDF. When PEDF was continuously infused into the low-fat mice over several days, insulin-stimulated glucose uptake by muscle cells was also reduced.

When they investigated whether blocking PEDF with a neutralising antibody could restore insulin sensitivity in obese mice, they found that this did not affect fasting blood glucose and insulin levels. However, it did improve the insulin sensitivity of the body in high insulin/high glucose situations.

 

What interpretations did the researchers draw from these results?

The authors say that their results demonstrate that changes in the size of fat cells in the body are accompanied by a change in the protein secretion from these fat cells. They say that this change in secretion is the important link between obesity and insulin resistance, and conclude that the release of PEDF from fat cells seems to have a direct effect upon body metabolism and increased resistance to the action of insulin.

The authors also go on to discuss the possible inflammatory effects of PEDF and its role in the breakdown of fats.

 

What does the NHS Knowledge Service make of this study?

The results suggest that insulin resistance in obesity, and hence the increased likelihood of glucose intolerance and diabetes, may be partly caused by PEDF (pigment epithelium-derived factor) released from fat cells.

This is worthy and interesting research, which has attempted to understand the possible biological mechanisms behind obesity and the increased risk of diabetes. However, as this is only an animal study, the situation may not be identical in humans.

At the current time it is unclear whether there are potential treatment implications (i.e. developing methods to block the action of PEDF to increase insulin sensitivity) but for now it is likely that this work will eventually lead to further research on the role and action of PEDF in human glucose intolerance. The actual reasons for increased fat cell secretion of PEDF in obesity, or whether there may be as yet unexplored factors involved in glucose metabolism, also remain unclear. Future research will be needed to explain this.
 
For the general population, the current advice remains unchanged: a combination of healthy diet and lifestyle plus regular exercise is the best way to avoid obesity and the risk of complications, such as type 2 diabetes.

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“Marriage trebles the risk of obesity” the Daily Express has warned, saying that new research shows that once couples marry they are three times as likely to become obese than people who live separately.

The study underpinning this story analysed data on several thousand heterosexual people in the US from adolescence onwards to establish the links between relationship status and obesity. It found an association between becoming married and new cases of obesity and also that obesity-related behaviour such as physical activity and television watching were more similar between couples that had lived together for longer.

Some newspapers have implied that marriage itself causes weight gain, but these confident conclusions fail to highlight the study’s limitations and the complexities that the researchers discuss. For example, there may be a range of other factors associated with both marriage and the risk of becoming obese. The researchers discuss the effects of shared environmental factors and assortative mating, the phenomenon whereby people select their partner on the basis of similarities or dissimilarities to themselves. The benefits that have been associated with marital status through other research, including a trend towards living longer, should also be highlighted.

 

Where did the story come from?

Dr Natalie The and Penny Gordon-Larsen from the University of North Carolina,  in the US carried out this study. It was funded by the National Institute of Child Health and Human Development, part of the US National Institutes of Health, and was published in the peer-reviewed medical journal Obesity.

 

What kind of scientific study was this?

Previous studies have shown that that there are benefits associated with marital status including reduced mortality. There is also a link between a person’s body mass index and their spouse’s which is thought to be due to a shared household environment or ‘assortative mating’ (or an interaction between the two), where individuals select partners with similar behaviours and body types.

To date research in this area has not clearly shown whether being married is associated with body weight and obesity. This retrospective cohort study assessed whether there was a link between ‘romantic relationships’ and obesity or obesity-related behaviours.

Researchers used data from the National Longitudinal Study of Adolescent Health, a prospective cohort study which began in American schools in 1994. In the first wave researchers interviewed 20,745 children in grades 7-12 and their parents. From this group there were a further two waves of research, with 14,438 subjects being re-interviewed in 1994 and a third wave of interviews for 15,197 in 2001 and 2002. During this third wave , participants were aged between18 and 27 years.

The third wave also included a ‘couples sample’ in which respondents recruited their ‘romantic partners’ to take the same interviews. Interviews at each time point included an assessment of height and weight, physical activity, time spent watching TV or playing computer games (<14 hours screen time per week or more), romantic relationship status and other factors including education, ethnicity and age.

There were two aspects to the study. In the first researchers investigated whether entering into a relationship or being in a longer relationship, compared with a shorter, was more likely to be associated with new cases of obesity.

To do this they compared whether a change from a single to a cohabiting or married status between waves II and III was more closely linked with weight gain than other status changes. They also looked at what effect duration of relationship had on obesity. They excluded pregnant women, Native Americans, people obese at baseline, and those who were missing important data, which left them with 6,949 people to analyse in this portion of the study. People with relationship status other than single or dating during wave II were included in the study which assessed the effects of a change in relationship status between waves II and III.

In the second cohort part of their study, the researchers assessed how closely obesity-related behaviours were linked within married couples, cohabiting couples and long-term cohabiting couples when compared to single people or those with shorter relationships.

They selected a random sample of couples of three months or more comprising a participant from wave III and their opposite sex partner, aged 18 or over. A total of 1,293 pairs of partners were available for analysis after excluding pregnant women and those who had missing data.

The researchers looked at whether the type of relationship (single, dating, cohabiting, or married) and duration of living together (not living together, 0.01 to 0.99 years, 1-1.99 years and 2 or more years) were linked to concordance in levels of physical activity (neither partner moderately-to-vigorously active, one partner active or both partners active), obesity (neither obese, one obese, both obese) or screen time (one, neither or both with 14 hours or less a week of screen time).

In both analyses, researchers adjusted their calculations to account for ethnicity, education and the age of parent or partner. Obesity was defined as a BMI of 30 or over.

 

What were the results of the study?

The study has several findings including:

• Men who went from single/dating at at wave II to married at III were 2.07 (95% CI 1.33 to 3.25) times more likely to become obese than those who went from single/dating to dating.
• Women making this same transition were 2.27 (95% CI 1.54 to 3.34) times more likely to become obese.
• Women who went from being single/dating at wave II to single at follow-up or single/dating to cohabiting were more likely to become obese. This association was not significant in men.
• The researchers report, but do not provide results, that women who went from single/dating at wave II to single at wave III were more likely to be persistently obese (i.e. obese at both time points).

In the couples sample, the study found that married and cohabiting partners were less healthy than dating romantic pairs in terms of physical activity, obesity and television/gaming time.

In the results about concordance, i.e. which characteristics couples shared, married couples were 3.3 times more likely than dating partners to share a similar obesity status to their partner than they were to have similar non-obesity status.

Married couples were also twice as likely to contain either one or two less physically active people than those who were dating. Both partners being sedentary was twice as common in cohabiting people than in those who were dating but not living together.

The researchers also found that men were more likely to have two or more weekly bouts of moderate-to-vigorous physical activity, but were also more likely to be the obese partner. Females were more likely than males to have less than 14 hours a week of screen time.

Compared to not living together, women who cohabited two or more years with their partner were twice as likely to be obese, while this association was not significant for men.

 

What interpretations did the researchers draw from these results?

The researchers conclude that duration of living with a romantic partner is associated with obesity and obesity-related behaviours, and that the transition from single/dating to cohabitation or marriage was generally associated with an increased risk of obesity.

The authors conclude that a link between negative, obesity-related behaviours was strongest for married couples and couples who had lived together for 2 or more years. They say that this observation could increase the chance that partners pass on high-risk behaviours to their offspring, and that targeting the shared household environment may be the best way to establish health behaviours and reduce obesity in young adulthood.

 

What does the NHS Knowledge Service make of this study?

This retrospective cohort study has relied on data from a large number of individuals to establish the links between relationship status, obesity and behaviours related to weight gain. However, the benefits that other studies have associated with marital status should also be highlighted,  as similar research suggests that romantic relationships reduce mortality and lower cigarette smoking.

There are also some limitations within this study that may undermine the suggestion that marriage itself is responsible for weight gain:

• The researchers acknowledge that their study sample is a unique, young, heterosexual population and as such their findings are not generalisable outside of these characteristics.
• The effects of a relationship lasting more than five years were not assessed in this study because too few of their sample met this criteria.
• There are factors that may change when a person enters a relationship, including diet, presence of children, weight control etc. and the part they may play are not captured in this research.
• One of the greatest limitations of cohort studies in establishing causation is the failure or inability to control for the many possible confounding factors that could be affecting the link between an exposure and an outcome. The researchers adjusted for pregnancy history, which slightly weakened the associations they saw and also suggested that other unadjusted factors may be playing a part.
• There is no way to fully account for ‘assortative mating’, the phenomenon whereby people choose partners similar or not similar to themselves. This in itself may explain why married couples (i.e. which may be viewed a type of relationship with more serious intentions than just dating) are more likely to be similar to each other in behaviour and BMI than those who are just dating. However, the researchers say that the fact that there is a link between a longer duration of sharing a household and higher obesity and obesity-promoting behaviours suggests that common environment in a partnership may play a ‘more significant role’ than assortative mating.

Notwithstanding the limitations outlined above, the study has found a link that deserves further investigation. There are likely to be many behaviours that change after marriage and understanding these and the links between them could help in tackling obesity.

Links To The Headlines

Marriage trebles the risk of obesity. The Express, July 7 2009

Getting married or moving in with a partner will make you fat, new research shows. The Daily Telegraph, June 11 2009

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