Lifestyle diseases are the ones we induce on ourselves by how we live our lives. They include being overweight/obese, insulin resistance, metabolic syndrome, type II diabetes (really a spectrum here), all leading to increased cardiovascular disease (and a number of other deadly diseases such as cancer, but to a lesser amount).
The easy solution to all of these is simple lifestyle changes – exercise and healthy eating. However, despite the well known ‘simple’, virtually no cost solutions most people fail. They want their cake and eat it too. They want to be healthy but they do not want to actually do anything about it.
A new paper might offer a potential solution.
Morino et. al., 2008 (PLOS one: freely available) examined if mild electrical stimulation (MES) combined with heat shock (HS) (not as bad as it sounds) could alleviate insulin resistance and obesity in a mouse model of diabetes.
Previous research with direct-field electrical stimulation have demonstrated decreased inflammation, better bone healing, reduction in pain, and inhibition of tumor growth (so don’t think of cell phones and electrical lines in this context of electrical stimulation) (see introduction of paper).
Twice a week the animals received 10 minutes of treatment (12 V (0.1 ms pulse duration) together with ‘heat shock’ at 42 degrees Celsius),(just for your information a hot tub is usually in the 38 to 40 range) or the individual treatments by themselves for a 12 – 15 week period. The researchers point out that the electrical simulations were ‘well tolerated and did not cause pain or annoyance behavior in the mice’ – the animals would sit still or doze off.
Two different strains of mice were used. One was fed a high-fat diet (which is typical for these types of paradigms) and in the other a leptin receptor deficiency causes them to overeat, and within one week after the initiation of the diet the treatment would start.
After 12 weeks on the diet (and treatment) the mice receiving the HS or the HS + MES had lower fasting glucose levels compared to the control group. However, fasted insulin levels were not lower in the HS group compared to controls, but the HS + MES group did have lower levels. In a glucose tolerance test (insulin sensitivity test) the HS + MES group had better glucose tolerance (quicker removal from blood stream) than the other groups. Another test for insulin resistance (HOMA-IR index – which is really fasting blood glucose x fasting insulin/22.5) was also significantly improved in the combined treated group.
Food intake or body weight did not differ between all the groups. Meaning that the treatment did not cause the animals to eat less – thereby the treatment positive effects are not simply due to a reduction of food intake.
They basically repeated the study for a longer period of time (25 weeks) to see if it would work in the more chronic setting. The combined treatment produced all the same results and additionally reduced the levels of TNF-alpha.
They also found that the serum levels of adiponectin (an adipocytokine secreted by fat tissue) were increased in the treated rats. Adiponectin is widely recognized to be inversely correlated with the amount of fat. Therefore, the researchers decided to investigate the amount of adipose tissue in the groups. White adipose tissue was reduced in the combined treated animals compared to the controls along with a reduction in the cell size of the adipocytes. More importantly visceral fat was decreased. Additionally, the brown fat (which burns calories to produce heat – called thermogenesis) expression of uncoupling protein one (UCP-1) was increased in the combined treated group, which would help explain the overall results.
In a second model of type II diabetes db/db mice (leptin receptor deficiency so they become obese) were used and the same overall results observed.
Interestingly, and intriguing is they tried the same treatment in standard fed mice which do not develop obesity and reported no differences in any of the above mentioned measurements (e.g. fasting glucose, insulin) between the control group and the HS + MES group.
They further tested which pathways they think the treatment is working through but I won’t go into those details here, but will present the authors summary of this part:
The effect of HS+MES on insulin signaling is likely through the capacity of electrical signal to trigger the activation of Akt (Fig. 8, ) and of HS to up-regulate Hsp72, which in turn inhibits JNK and activates the insulin signaling pathway (Fig. 4C, Fig. 9 [24,41]). Although the core body temperature of the mice was less than 42 C, the method of mild HS that we used was enough to induce the expression of Hsp72 (Fig. 4D).
The HS + MES treatment started within one week after the initiation of the high fat diet. We do not know if this treatment would ‘reverse’ the effect if started in the normal human situation – after they have become obese and insulin resistance or diabetic. However, in the db/db mice because of the genetic reduction in leptin receptor it could be argued the animals are on their way already when the treatment started (but I am not familiar enough with this transgenic strain to fully comment).
An interesting experiment would be too test this treatment further along the progression of insulin resistance/diabetes/obesity. But we know exercise and serious changes in diet can have dramatic effects on these conditions, so it is still possible that the HS + MES could work even if started after the condition is full blow – but it wasn’t tested in this paper.
Could we translate this to humans?
The authors point out the low levels of electrical stimulation as well as heat shock are used in the clinical setting. However, I would point out in both of these situations (from the references I read) the treatments were for relatively short time periods. In the treatment outlined above for the human situation, assuming the individuals are going to continue with an unhealthy lifestyle it would suggest they would have to continue with the treatment indefinitely. The long term health consequence would have to be studied – but it appears to be positive based on the above results as the animals were treated for a relatively long period of time (and no negative effects observed in the normally fed animals – but also no positive effects).
Of course in reality the goal is to live a healthy lifestyle so you do not develop these lifestyle linked diseases – but if you are unable to live a healthy lifestyle this might an option in the future – but it should be a last action of last resort.
It would be good to know if the brown fat is an important part of this process, as humans don’t really have much (any?) brown fat as adults. Though there is some recent evidence to suggest that we might be able to push white adipocytes to become brown ones…so maybe it doesn’t matter too much.
Interesting comment regarding brown fat in humans (I have 3/4 written a post about that subject). I always thought/read/learned that human adults do not have brown fat – but as you mention far as I can ascertain it seems that human adults do have brown fat (or at least some of them) (so much for what we had previously been taught). And yes you are correct a very recent paper suggests that white fat cells can be ‘pushed’ toward brown fat – but there is more of a developmental route to brown fat via myogenic precursors (the cells that normally make muscles).
So yes a great deal more to study – but an intriguing possibility.