Monday, 3 February 2014

Plasma leptin levels and autism: a growing consistency?

Increased levels of leptin in cases of autism was a primary finding described in the paper by Rodrigues and colleagues [1] as part of their analysis of the adipokines, the cell signalling molecules secreted by fat (adipose tissue) (see this paper by Trayhurn and colleagues [2] for quite a good overview). Not for the first time I might add, that elevations in levels of leptin have been talked about with autism in mind [3]. Indeed if you want even more evidence of a possible link, see also the paper by Blardi and colleagues [4] and their findings in relation to cases of Rett syndrome [5]. Oh and elevations in leptin in cases of autism crosses countries too.
Have parasol will travel @ Wikipedia

From the beginning, leptin is an adipokine which are cytokines. There is quite a bit of chatter about leptin being more of a proinflammatory cytokine and in particular, it's similarity to another inflammatory-related cytokine, IL-6 (see here for a previous post on this molecule). It's also worthwhile noting that leptin has an emerging role in the shift in immune function toward a T-helper1(Th1) response (see here for some background on Th1 and Th2 responses) which potentially brings into play an autoimmune element. I've actually talked about leptin before on this blog and some preliminary findings correlating leptin levels and fatigue scores in cases of Chronic Fatigue Syndrome (CFS).

Quite a lot of discussion has focused on the role that leptin also plays in regulating dietary intake and its suggested link with body weight and obesity; circulating leptin levels correlating well with the proportion of body fat. It's well beyond the scope of this post or indeed my very rudimentary knowledge of this area, but there is quite a lot of evidence to suggest that deficiencies in leptin lead to severe obesity as a function of it's role in the activation of satiety mechanisms. That being said it's not all plain scientific sailing as per the review by Paracchini and colleagues [6] (open-access) on the genetics of leptin and obesity. Obese people generally have high leptin levels, as a function of having more fat, which has led to some speculation about the notion of leptin resistance (see the paper from Myers and colleagues [7] for more information).

That energy homeostasis role aside - which may nevertheless be important when it comes to medication-induced weight gain in autism [8] - the elevations in plasma leptin levels reported by Rodrigues et al (and other authors) may be important. As per the Stringer paper [9] which was the source material for my leptin-CFS post: "Multiple studies have demonstrated elevated levels of circulating leptin in chronic inflammatory conditions". A quick trawl of PubMed leads me to believe that there may be indeed be an important role for leptin in the process of inflammation as per articles like this one and this one. That also quite a nice correlation between leptin and more traditional markers of inflammation, such as C-reactive protein (CRP) have been discussed [10] is added fodder for this assertion. Oh, and just in case you're wondering, CRP has also been examined with autism in mind (see this post and this post).

The implication therefore is that elevated levels of leptin present in cases of autism might be an important sign of immune processes, particularly those related to inflammation. I can't say whether this means autism per se is 'inflammatory' in those cases of elevations or whether we're talking about some inflammatory-mediated comorbidity for example. Nonetheless, there is a growing consistency in the results obtained so far which is crying out for more detailed investigation controlling for weight, body fat and body mass index (BMI). This call likewise resonates with other conditions too including bipolar disorder and schizophrenia albeit without over-generalising and again taking into account the important effect of medication.

And just in case you're wondering about possible ways and means to reduce leptin levels, well without any medical or clinical advice being given, how about a spot of exercise for starters?

To close, having recently watched the excellent Dave Grohl documentary about Sound City (UK viewers if they're quick, can catch it on the BBC iPlayer), a song about someone's wife calling?

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[1] Rodrigues DH. et al. Changes in Adipokine Levels in Autism Spectrum Disorders. Neuropsychobiology 2014;69:6-10

[2] Trayhurn P. et al. Adipose Tissue and Adipokines—Energy Regulation from the Human Perspective. J Nutr. 2006; 136: 19355-19395.

[3] Ashwood P. et al. Brief report: plasma leptin levels are elevated in autism: association with early onset phenotype? J Autism Dev Disord. 2008 Jan;38(1):169-75.

[4] Blardi P. et al. Variations of plasma leptin and adiponectin levels in autistic patients. Neurosci Lett. 2010 Jul 19;479(1):54-7.

[5] Blardi P. et al. Long-term plasma levels of leptin and adiponectin in Rett syndrome. Clin Endocrinol (Oxf). 2009 May;70(5):706-9.

[6] Paracchini V. et al. Genetics of Leptin and Obesity: A HuGE Review. Am. J. Epidemiol. 2005; 162: 101-114.

[7] Myers MG. et al. Obesity and Leptin Resistance: Distinguishing Cause from Effect. Trends Endocrinol Metab. 2010 November; 21(11): 643–651.

[8] Nurmi EL. et al. Moderation of antipsychotic-induced weight gain by energy balance gene variants in the RUPP autism network risperidone studies. Transl Psychiatry. 2013 Jun 25;3:e274.

[9] Stringer EA. et al. Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology. Journal of Translational Medicine 2013, 11:93

[10] Shamsuzzaman ASM. et al. Independent Association Between Plasma Leptin and C-Reactive Protein in Healthy Humans. Circulation. 2004;109:2181-2185.

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ResearchBlogging.org Rodrigues D.H, Rocha N.P, Sousa L.F.C, Barbosa I.G, Kummer A, & Teixeira A.L (2013). Changes in Adipokine Levels in Autism Spectrum Disorders Neuropsychobiology