Obesity Compounds Pain in Fibromyalgia
As blogged before, overweight and obese patients frequently present with fibromyalgia, characterized by chronic pain, fatigue and depressed mood. A paper by Akiko Okifuji from the University of Utah, Salt Lake City, just published in the Journal of Pain, examines the relationship between fibromyalgia and obesity in pain, function, mood, and sleep. The study examines the impact of obesity on hyperalgesia, symptoms, physical abilities, and sleep in 215 fibromyalgia patients, who also underwent tender point examination, physical performance testing, and 7-day home sleep assessment. Almost 50% of participants were obese and an additional 30% were overweight. Obesity was positively related to greater tender point sensitivity, reduced physical strength and lower-body flexibility, shorter sleep duration, and greater restlessness during sleep. The results confirmed that obesity is a prevalent comorbidity of fibromyalgia and the authors suggest that weight management may need to be incorporated into treatments. In the paper, Okifuji and colleagues also discuss several potential mechanisms linking obesity to fibromyalgia including alterations in the endogenous opioid system, the endocrine system, and systemic inflammation, whereby adipose-tissue derived cytokines may enhance central sensitization. Clinicians should be aware of the relationship between excess weight and fibromyalgia, which can often pose an important contributor to weight gain and a major barrier to weight management. AMS Edmonton, Alberta Okifuji A, Donaldson GW, Barck L, & Fine PG (2010). Relationship Between Fibromyalgia and Obesity in Pain, Function, Mood, and Sleep. The journal of pain : official journal of the American Pain Society PMID: 20542742
Obesity, Trauma, and Inflammation
Today, I am attending the 8th World Congress on Trauma, Shock, Inflammation and Sepsis in Munich, Germany. Interestingly, this conference features a whole series of seminars on the interdisciplinary management of obesity (under the rather unfortunate title ‘Fat Man – We Will Help You’ [sic]). I have been invited to chair and speak at the session on medical therapy, but there are also sessions on adipose tissue biology, perioperative management, bariatric surgical procedures, and the emergency management of bariatric patients. As I often say in my presentations to colleagues: it does not matter what discipline in medicine you practice – you will be seeing an increasing number of heavier patients with their own issues and complications. The fact that a world conference on trauma should devote this much time to sessions on obesity assessment and management is clearly to be commended in the light of the global obesity epidemic. The more all health professionals learn and understand the complexities and problems posed by heavier patients, the better we can serve this particularly vulnerable patient population. AMS Munich, Germany
Fat Storage Enzyme May Keep Fat Mice Healthy
Obesity is often described as a state of low grade inflammation. Activated macrophages (white blood cells) in adipose tissue play an important role in this inflammatory response by secreting a number of pro-inflammatory molecules (cytokines) that can promote the development of insulin resistance and other complications of obesity. Previous studies have shown that the “glitazone” class of antidiabetic agents can suppress inflammatory macrophage activation and can also increase the expression of an DGAT1 (triacylglycerol (TG) synthesis enzyme acyl CoA:diacylglycerol acyltransferase 1), an enzyme that makes it easier for fat cells and macrophages to store excess fat. Now a paper by Suneil Koliwad and colleagues from the Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA, published in this weeks’ issue of the Journal of Clinical Investigation, provides further evidence that increasing activity of DGAT1 in adipocytes and macrophages may protect animals from the pro-inflammatory effects of obesity. The researchers found that although mice overexpressing DGAT1 in both macrophages and adipocytes were more prone to weight gain, they did not show signs of the inflammatory response commonly seen with diet-induced obesity. Through a series of experiments, the researchers were able to establish that DGAT1 is indeed necessary to protect against this inflammatory response, thereby raising the question of wether stimulation of this enzyme may also protect against the complications of obesity in humans. Thus, although this research may not lead to new ways of preventing or reducing obesity, it may open new avenues for attenuating some of the health consequences related to excess weight. AMS Copenhagen, Denmark
Obesity and Fibromyalgia: a Painful Barrier to Weight Loss?
To anyone regularly dealing with overweight and obese patients, the frequent association between excess weight and chronic musculoskeletal pain is no secret. This association is particularly true for the rather enigmatic syndrome of fibromyalgia, characterised by the presence of generalized pain in muscle and joints, often associated with fatigue, poor sleep, and depression. Patients typically present with exquisite tenderness over discrete anatomical points, commonly referred to as tender points. While there is still much debate around the exact etiology or even the exact diagnostic criteria (e.g. number of tender points) for fibromyalgia, there is no doubt that the presence of this syndrome can prove a major barrier to weight management. Indeed, it is not at all clear whether there may in fact be an etiological link between fibromyalgia and obesity. As outlined in a paper by Akiko Okifuji and colleagues from Salt Lake City, UT, published last year in Clinical Rheumatology, 70% of fibromyalgia patients in their study were overweight or obese and presented with elevated levels of IL-6, catecholamines, cortisol, and CRP, all of which are common findings in obese patients. Furthermore, the patients with fibromyalgia, as do obese patients, presented with reduced sleep duration and efficiency. Based on these commonalities, Okifuji and colleagues concluded that excess weight and obesity may well play a role in fibromyalgia and related dysfunction. Interestingly, in 2008, Alan Saber and colleagues published an article in Obesity Surgery describing a significant improvement in pain score and points of tenderness in patients with fibromyalgia who underwent laparoscopic Roux-en-Y gastric bypass surgery. Based on these findings, the authors suggested that weight loss may be an important treatment modality for severely obese patients with this syndrome. Whether or not less drastic approaches to weight management can provide benefits remains to be seen. Nevertheless, there have been reports of limited response to education, exercise, and psychological interventions. Thus, currently accepted non-pharmacological treatments for fibromyalgia remain rather limited. Recently, a Cochrane review concluded that duloxetine is efficacious for treating pain in fibromyalgia and another systematic review found evidence that gabapentin and pregabalin can also reduce pain in these patients. Nevertheless, fibromyalgia continues to be a common but largely undertreated problem in overweight and obese patients and can often pose a significant barrier to increasing physical activity or modifying ingestive behaviour. As blogged before, assessment for muskuloskeletal pain should be a regular and essential feature of any assessment for overweight and obesity. I very much look… Read More »
Will Immunotherapy Provide a New Treatment for Obesity?
Obesity is widely associated with low grade inflammation and previous studies have noted increased incidence of allergic responses in obese individuals pointing to a possible role of immune response in the regulation of metabolism and body weight. Last week Nature Medicine published three separate articles, which together may well herald in an entirely new area of obesity research: immunometabolism or metabolic immunology. Although all studies reports finding in mouse models of obesity and diabetes, their observations may well have important implications for human obesity. In the first study, Satoshi Nishimura and colleagues from the University of Tokyo show that CD8+ effector T cells play an important role in macrophage recruitment and adipose tissue inflammation. They not only found that large numbers of CD8+ T cells infiltrated obese epididymal adipose tissue in mice fed a high-fat diet (while there was a depletion of CD4+ T ells), but also that this infiltration preceded the accumulation of macrophages in fat tissue. On the other hand immunological and genetic depletion of CD8+ T cells lowered macrophage infiltration and adipose tissue inflammation and ameliorated systemic insulin resistance. Coculture and other in vitro experiments revealed a vicious cycle of interactions between CD8+ T cells, macrophages and adipose tissue. These results support the notion that CD8+ T cells have an essential role in the initiation and propagation of adipose inflammation. In the second study, Markus Feuerer and colleagues from Harvard Medical School, Boston, USA, showed that CD4+ regulatory T cells with a unique phenotype were highly enriched in the abdominal fat of normal mice, but, similar to the observation by Nishimura and colleagues, their numbers were strikingly and specifically reduced in insulin-resistant models of obesity. Loss-of-function and gain-of-function experiments revealed that these regulatory T cells influenced the inflammatory state of adipose tissue, insulin resistance, and glucose uptake. In the third study, Shawn Winer and colleagues from The Hospital for Sick Children, University of Toronto, Canada, showed that immunotherapy with CD4+ (but not CD8+) T cell transfer into lymphocyte-free obese mice reversed weight gain and insulin resistance. In other obese mice, brief treatment with CD3-specific antibody or its F(ab’)2 fragment reversed insulin resistance for months, despite continuation of a high-fat diet. Together these papers not only document the important role of immune response in the development of obesity and its complications but also identify a number of novel targets and strategies that could be harnessed to treat obesity… Read More »
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