Healthy obesity

What is Healthy Obesity?

Although obesity is a major risk factor for cardiovascular disease and type 2 diabetes mellitus, about a third of obese individuals maintain healthy cardiometabolic profiles; this phenotype of healthy obesity may be linked to the location of adipose tissue and the metabolic characteristics of the fat. Some data also suggest that weight loss by healthy obese subjects may have an adverse impact on their favorable cardiometabolic profile.

Why is Healthy Obesity Worthwhile investigating?

Investigating why H.O can't be regarded as simply obesity e.g. treatment problems, some weight losing methods actually detrimental to H.O individual

Waste of money to treat all H.O individuals as simply obese?

The Cause of Healthy Obesity?

Proposed Mechanistic Determinants of the Healthy Obese Phenotype

Adipose tissue is an endocrine organ, releasing several inflammatory cytokines and expressing endocrine hormone receptors. The location of adipose tissue, the histological characteristics of adipose tissue and its metabolic activity may be more relevant than its total mass with regards to the healthy obese phenotype, and they may play a role in determining the cardiometabolic health of obese individuals .

Adiponectin and Healthy Obesity

Adiponectin is a protein hormone which is secreted into the bloodstream from adipose tissue and modulates several metabolic processes, including fatty acid catabolism and glucose regulation. The level of adiponectin in the bloodstream is inversely correlated to the percentage of body fat in adults. It is associated with the suppression of metabolic processes that can lead to obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease (NAFLD). Diabetics tend to have reduced levels of the hormone and levels of adiponectin are significantly increased with weight loss. Other metabolic effects of adiponectin are: decreased gluconeogenesis and increased glucose uptake; lipid catabolism; protection from endothelial dysfunction; insulin sensitivity, and control of energy metabolism. Hypoadiponectinaemia, therefore, is an independent risk factor for metabolic syndrome and type 2 diabetes mellitus– two conditions associated with an unhealthy metabolic profile of obese individuals.

There is an inverse relationship between body mass index (BMI) and concentrations of adiponectin in both humans and animals. However, in ob/ob mice - mutant mice that eat excessively and become obese - overexpression of adiponectin in adipose tissue increased plasma adiponectin concentrations, keeping them in a physiological range. This increase resulted in significant weight gain and reduced hyperglycaemia and amended metabolic abnormalities. These findings suggest a role of variable plasma adiponectin concentrations in the pathophysiology of the healthy obese phenotype. Data from one recent study shows that lack of suppression of adiponectin concentrations is independently associated with the metabolically healthy profile of certain obese individuals .

One study found that 20% of individuals with a BMI greater than 40kg/m2 had adiponectin concentrations on average higher than those of subjects with a normal BMI. Obese women and men with adiponectin concentrations >12.49mg/l and >8.07mg/l respectively, were more likely to be metabolically healthy. These results were proven to be significant in a logistic regression model after controlling the effect of insulin, age, and waist circumference. Thus, some obese individuals have plasma adiponectin concentrations similar to those of normal BMI subjects, and this may contribute to the metabolically healthy obese phenotype .

Location of Adipose Tissue

Both central adiposity and ectopic fat (fat found in lean tissue) are thought to be associated with the role of fat location in healthy obesity. Some studies have found that healthy obese individuals have smaller waist circumferences or lower levels of abdominal visceral fat (VAT) than metabolically unhealthy individuals. This is not surprising as central visceral fat is drained into the portal circulation and contributes to insulin resistance and dyslipidaemia, two factors associated with cardiovascular risk and metabolic disturbances . However, other studies produced data suggesting otherwise, and found that there were no differences in central obesity between healthy and at-risk obese individuals.

High levels of subcutaneous adipose tissue (SAT) have been found in some studies to be protective against atherosclerosis, independent of levels of VAT, suggesting a role for SAT in the healthy obese phenotype. However, other studies have found that high levels of SAT and VAT contribute to elevated CVD risk factors, and no differences in SAT levels were found between healthy and at-risk obese individuals. This could be due to the suggested modifying effects of VAT on SAT's effects on metabolic profile; high levels on SAT contribute to development of the metbolic syndrome when paired with loe VAT levels, but seem to be protective when paired with high levels of VAT .

Victoria Catherine Pickard 19:57, 31 October 2011 (UTC)

Does Healthy Obesity need to be treated?

Having been characterised as ‘Healthily Obese’ using the above criteria, what treatment strategy, if any, should be used? The widely accepted intervention for all obese people is weight loss (National Institutes of Health, 1998), however is this an appropriate and efficacious option for this minority phenotype of the obese population? If so, what impact would this have in their health in general, but more specifically on their cardio-metabolic risk factors?

Evidence for interventions A variety of studies have been carried out to ascertain whether Metabolically Healthy Obese (MHO) subjects gain any benefit from weight loss. There are three principle strategies for reducing body mass: increasing exercise levels, hypoenergetic diets and surgery (e.g. Laproscopic Adjustable Gastric Banding [LAGB]). Studies have been carried out recently to see the impact of these methods on the MHO. In a 2008 study (Karelis et al, 2008), when participants were put on an energy-restricted diet for a 6 month period (with physical activity levels limited), both the MHO and at-risk groups showed a significant increase in insulin sensitivity, prompting the paper to call for a ‘one size fits all’ approach to obesity intervention. It has been shown that the use of an energy-restricted diet causes a significant increase in insulin sensitivity in MHO subjects, whilst the same study also highlighted signs of sub-clinical vascular disease, which if left untreated could lead to consequences in later life (Janiszewski et al, 2010). An interesting recent study (Sesti et al, 2011) into the impact of gastric banding and a hypocaloric diet on both MHO and at risk obese populations concluded that some significant factors were higher in the at risk group, such as, waist circumference, 2hr OGTT and insulin levels. There was no difference in other significant measurements such as total and HDL cholesterol.

However other recent published literature contradicts some of this evidence. When lifestyle was modified by varying the level of exercise programme the participants were submitted to, there was no significant difference in insulin sensitivity or any other major markers. There was no improvement in cardio-vascular risk profile in the MHO group (Kantartzis et al, 2011). Other studies back up these findings, showing that there is at best a moderate increase in insulin sensitivity with a hypocaloric diet. There is increasing evidence that the method by which weight is lost may be crucial to the outcome for the patient. Weight loss by diet modification and surgery has been proven to be overall beneficial, whilst the use of a exercise programmes has shown less efficacy (Perseghin, 2008). Healthy obesity treatment is a targeted area of current research, with larger trials necessary to improve reliability and distinguish the true impact of various strategies on the patient.

The healthy obese phenotype makes up a reputed 30% of all obese people (McLaughlin et al, 2007). Since an estimated 9% of the NHS annual budget is spent on treating obesity and its effects, whether or not an intervention is necessary for this subset of high adiposity individuals is a pressing issue. Surely for such a proven heterogeneous obese population, the current ‘one size fits all’ approach cannot be the most economical and patient-centred option.

Criticism of Current Data - Does the Healthy Obesity Phenotype Actually Exist?

Investigating whether or not H.O is a genuine phenotype or has this subgroup emerged as a result of methodological/ measurement issues? Are these people healthy and truely obese/ are they obese yet truely healthy?

Conflicting findings of meta-analyses from NEJM and American heart journal etc. the impact of adjusting for physical activity and the role of other parameters. eg. lack of any the metabolic syndrome criteria & no insulin resistance counts as healthy. non metabolic morbidity.

or if that overlaps too much with someone else's section I could cover:

the role of ethnicity: A higher proportion of black healthy obese? Possible underlying mechanism?

Losing weight can be harmful for the healthy obese: (Gaesser 1999)Tijmen van Slageren 18:38, 24 October 2011 (UTC)