Disclaimer: no actual weight was lost in this study! Nevertheless, according to a Han Kyungsun and colleagues, in a paper published in Molecular Nutrition and Food Research, daily ingestion of fermented (but not unfermented) kimchi may result in a potentially beneficial change in the gut bacteriome profile with changes in the expression of multiple metabolic pathways (at least in circulating blood cells).
This study on 8-weeks of fermented vs. unfermented kimchi in 24 women with obesity, was prompted by the widely held assumption that fermented preserves (e.g. kimchi, sauerkraut, etc.) can have positive metabolic effects and has optimistically been linked to weight loss (although evidence for this is rather anecdotal at best).
Be that as it may, the fact that the researchers did find an effect on the relationship of firmicutes to bacteroides populations in the gut at least demonstrates that fermented foods (in this case kimchi) can indeed have a significant on gut bacteria.
How and if this results in any clinically relevant metabolic changes remains to be seen.
With all of the recent interest in the gut microbiota as a mediator of systemic inflammation and metabolic disease, it was only a matter of time before researchers would begin targeting pro-inflammatory pathways in the gut to change metabolism.
A proof-of-principle, that this is indeed possible, is presented by Helen Luck and colleagues from the University of Toronto in a paper published in Cell Metabolism.
Using mice models, the researchers not only show that a high-fat diet can alter the gut immune system but also that the chronic phenotypic pro-inflammatory shift in bowel lamina propria immune cell populations is reduced in genetically altered mice that lack beta7 integrin-deficient mice (Beta7null), a driver of gut inflammatory response.
Further more, treatment of high-fat-fed normal mice with the local gut anti-inflammatory agent 5-aminosalicyclic acid (5-ASA), reverses bowel inflammation and improves metabolic parameters including insulin resistance (although it had no effect on body weight).
These beneficial effects are are associated with reduced gut permeability and endotoxemia as well as decreased visceral adipose tissue inflammation.
Moreover, treatment with ASA also improved antigen-specific tolerance to luminal antigens.
Thus, as the authors conclude,
“…the mucosal immune system affects multiple pathways associated with systemic insulin resistance and represents a novel therapeutic target in this disease.”
Clearly gut inflammation both in relationship to gut microbiota as well as response to dietary factors is likely to be a hot topic in obesity and metabolic research for the foreseeable future.
Warning – this is not an April Fool’s post! Rather, it is a follow up to yesterday’s post warning that even “lifestyle” or behavioural interventions can have adverse effects – at least for some people.
Point in case, is this paper by Claude Bouchard and colleagues, published in PLOS one back in 2008, clearly documenting clinically significant harmful metabolic effects of exercise in some individuals (about 1 in 10).
I would probably have disregarded this paper, except for the fact that the authors include a who-is-who of exercise experts, Steven Blair, Timothy Church, Nathan Jenkins, just to name a few. These are all enthusiastic supporters of increasing physical activity with rock-solid expertise in exercise physiology.
Their findings are based on completers from six exercise studies involving a total of 1,687 men and women.
Although metabolic parameters in general improved (as expected) in most participants, 8.4% had an adverse change in fasting insulin, 12.2% has a clinically significant increase in resting systolic blood pressure, 10.4% had a relevant increase in fasting triglycerides, and 13.3% had a reduction in HDL-Cholesterol. About 7% of participants experienced adverse responses in two or more risk factors.
While the authors note that the explanation for these findings remain unclear,
“…the adverse response traits are not explained by prior health status of subjects, age, amount of exercise imposed by the program, or lack of improvement in cardiorespiratory fitness. No evidence could be found for the hypothesis that adverse responses were the result of drug-exercise interactions.”
Which brings me back to yesterday’s post, that even the best meant behavioural recommendation (in this case “move more”) can carry risks for some individuals and may require personalised and ongoing monitoring.
Funnily enough, I would imagine that if you packed exercise into a pill with these types of “adverse effects”, I wonder if the FDA would actually let you sell it.
Incidentally, Claude Bouchard will be one of the key note speakers at the upcoming 4th Canadian Obesity Summit in Toronto, April 28-May 2. I’m sure he will be presenting some of these data and the fascinating genetic studies that have since been done on this issue.
Hat tip to Morgan Downey for reminding me of this study.
To preregister for the Canadian Obesity Summit click here
Last week at the 8th Annual Obesity Symposium hosted by the European Surgery Institute in Norderstedt, one of the case presentations included an individual with type 1 diabetes (no insulin production), who had gained weight and subsequently also developed increasing insulin resistance, the hallmark of type 2 diabetes.
In my discussion, I referred to this as 1+2 diabetes, or in other words, type 3 diabetes.
Unfortunately, it turns out that the term type 3 diabetes has already been proposed for the type of neuronal insulin resistance found in patients with Alzheimer’s disease.
As discussed in a paper by Suzanne de la Monte and Jack Wands published in the Journal of Diabetes Science and Technology,
“Referring to Alzheimer’s disease as Type 3 diabetes (T3DM) is justified, because the fundamental molecular and biochemical abnormalities overlap with T1DM and T2DM rather than mimic the effects of either one.”
These findings have considerable implications for our understanding of Alzheimer’s disease as a largely neuroendocrine disorder, which may in part be amenable to treatment with drugs normally used to treat type 1 and/or type 2 diabetes.
In retrospect, I believe, whoever came up with the term type 3 diabetes for Alzheimer’s disease, should perhaps have called it type 4 diabetes, given that the 1+2 diabetes is now increasingly common (and well studied) in patients with type 1 diabetes, who go on to develop type 2 diabetes (which, as discussed at the symposium responds quite well to bariatric or “metabolic” surgery).
That there are no easy solutions to obesity and managing your weight is challenging at the best of times. But trying to find manage it without understanding even the basics of how your body works to defend its weight is hopeless at best.
A sort paper by Christopher Ochner and colleagues, published in The Lancet Diabetes and Endocrinology, succinctly describes the challenges, and appeals to clinicians (and decision makers) to take this problem seriously (instead of trivialising it as a simple “lifestyle” issue).
“Many clinicians are not adequately aware of the reasons that individuals with obesity struggle to achieve and maintain weight loss, and this poor awareness precludes the provision of effective intervention.”
As readers of these pages are well aware,
“Irrespective of starting weight, caloric restriction triggers several biological adaptations designed to prevent starvation. These adaptations might be potent enough to undermine the long-term effectiveness of lifestyle modification in most individuals with obesity, particularly in an environment that promotes energy overconsumption.”
But is is not just about the body’s defense mechanisms.
“Additional biological adaptations occur with the development of obesity and these function to preserve, or even increase, an individual’s highest sustained lifetime bodyweight. For example, preadipocyte proliferation occurs, increasing fat storage capacity. In addition, habituation to rewarding neural dopamine signalling develops with the chronic overconsumption of palatable foods, leading to a perceived reward deficit and compensatory increases in consumption.”
“…improved lifestyle choices might be sufficient for lasting reductions in bodyweight prior to sustained obesity. Once obesity is established, however, bodyweight seems to become biologically stamped in and defended. Therefore, the mere recommendation to avoid calorically dense foods might be no more effective for the typical patient seeking weight reduction than would be a recommendation to avoid sharp objects for someone bleeding profusely.”
As the authors point out,
“…there is now good evident that these biological adaptations often persist indefinitely, even when a person re-attains a healthy BMI via behaviourally induced weight loss….Thus, we suggest that few individuals ever truly recover from obesity; individuals who formerly had obesity but are able to re-attain a healthy bodyweight via diet and exercise still have ‘obesity in remission’ and are biologically very different from individuals of the same age, sex, and bodyweight who never had obesity.”
To overcome these biological adaptations it is not enough to appeal or rely on will-power alone to sustain long-term weight loss. Rather, treatments need to address these biological adaptations and homeostatic mechanisms, which is exactly what anti-obesity drugs or surgery does.
Thus, the authors have the following advice for clinicians:
“Specifically, clinicians should be proactive in addressing obesity prevention with patients who are overweight and, for those who already have sustained obesity, clinicians should implement a multimodal treatment approach that includes biologically based interventions such as pharmacotherapy and surgery when appropriate.”
“We urge individuals in the medical and scientific community to seek a better understanding of the biological factors that maintain obesity and to approach it as a disease that cannot be reliably prevented or cured with current frontline methods.”