Fat Is More Than Just Flab

Obesity isn’t only increased weight: hormones and behavior change as well.

Posted Mar 22, 2016

Not so many years ago, fat was considered a rather uninteresting tissue.  It was thought of as a storehouse for excess or reserve energy, and a sort of blanket against the cold.  So whales and penguins had lots of it, and fat people tended to feel the cold less than skinny ones.   They also lasted longer under conditions of starvation.

Then the story began to change. It was noticed that, whilst fat was mostly the usual white greasy stuff, some animals had a second sort, brownish in colour. This remained a curiosity until someone put a small rodent (they have quite a lot of brown fat) into a cold box and recorded its infrared signature.  The patches of brown fat glowed!  Brown fat acted as central heating, and was activated by exposure to cold. It was quickly determined that this was controlled by the autonomic nervous system, which deals with stressful events such as exposure to cold. But adult humans don’t have much brown fat (babies have some along their back and neck). It’s particularly useful for small animals with large surface area to body mass ratios that lose heat rapidly in cold environments. By comparison, white fat seemed rather boring.

Under the microscope, white fat cells don’t look as if they do much other than store great globs of fat.  So it was astonishing when it was discovered that white fat was a major endocrine organ.  Nobody quite believed it when the hormone leptin (from the Greek for ‘thin’) was shown to be secreted by white fat and turned out to be a down-regulator of long-term food intake. The more white fat, the more leptin: so it seemed to play a role in controlling body weight according to the amount of fat an individual carries. Mutations in either it or its receptors resulted on massive obesity in mice. There are comparable reports in humans; rare mutations in leptin result in massive overeating and pathological obesity.  Even lesser degrees of obesity, the kind that citizens of the USA and UK now see regularly on their streets (USA: 33%; UK: 26%), may be associated with partial insensitivity to leptin, though how this occurs is still uncertain.

Interestingly, leptin may reduce the hormonal response to stress, and low levels have been associated with an increased risk of developing dementia.  White fat is now known to produce several other hormones  (adiponectin is one) as well as cytokines implicated in immune activity. It also, in women,  increases the amount of estrogen,  because white fat contains an enzyme that converts other steroids to estrogen. This is one reason why obesity is a risk factor for certain cancers (eg the breast). But there's an upside: increased estrogen in fatter women may protect them against loss of bone density (osteoporosis). Far from being a dull, rather inert tissue, white fat has become very interesting indeed! It's not just a biological larder that doubles as a duvet.

Much of the experimental work on learning, memory and reward is based on animals - usually rats - carrying out operant procedures for food.   Psychology has contributed much to our understanding of why we eat, what we eat and why some people or animals may become obese.  Sadly, attempts to use leptin or its analogues as weight-reducers have largely failed; and the hope that it might be important in eating disorders such as anorexia has not been fulfilled.  Anorexia is not simply the result of either too much leptin, or over-sensitivity to its action, which was a hope at one time. The realisation that white fat is a very active tissue means that obesity is more than a weight problem, it's an endocrine disorder as well. This may explain, at least partly, why obesity is a risk factor for diabetes, cardiovascular disease, breast and liver cancer, asthma and age-related cognitive impairment - either alone, or as part of the 'metabolic syndrome'.  It may also reduce immune function, and there are indications that maternal obesity may increase the risk of attention-hyperactivity disorder, autism spectrum disorders, anxiety, depression and eating disorders in offspring.

A mother's leptin may have other long-lasting consequences for her child. If a women lives in a situation where food is chronically scarce, then her offspring needs to prepare to be born and raised in this environment. It is likely to be tough. So signals from the mother, principally (but not exclusively) her leptin levels, cause the developing fetus to adapt its metabolism to future hardship. It becomes better able to resist periods of starvation  etc.  But there are downsides to this.   If the environment should change (for example, become less demanding) then the growing child, and the later adult, is less able to deal with a greater abundance of food.  This will result in an increased risk for  number of disorders, including heart disease, obesity and diabetes. The child, it is thought, has developed a 'thrifty phenotype', an adaptation for a tough life, but somewhat mal-adaptive for a better one. This idea is still controversial, and there are arguments about whether this adaptation is for the child's or the mother's benefit.  However, it does seem to be the case that humans, like all other animals, have developed defense mechanisms against too little food, a common situation in nature, but are much less able to deal with too much, a rare event in the lives of most animals. Incidentally, this may be one reason why it's so easy to put weight on, but much harder to lose it. 

Most of the work on the hormones and other active substances produced by fat is being done by physiologists or medics.  But fat is such an active tissue, producing so many compounds that can have an impact on behavior, that it's time psychology took a new, hard, look at fat.  Being overweight may have implications that go wider than we currently suspect. Disturbance in hormone sensitivity may help explain why people become obese, but the subsequent changes in hormone secretion and function may also explain why obesity itself is a major metabolic disturbance, and why it is such a hazard to good health, long life and psychological well-being.

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