The gut microbiotia and obesity

Humans can’t process and absorb all of their consumed food. However our guts are home to trillions of commensal bacteria which help break down food our own cells cannot, allowing us to reap the benefits. Upwards of 90% of these bacteria fall within two groups called the Bacteroidetes and the Firmicutes. Research released in 2008 suggests that the proportion of these groups “is linked to the risk of becoming obese.”

Washington University scientists: Ruth Less, Peter Turnbaugh and Jeffrey Gordon, tested the hypothesis on mice that lack the hormone leptin. Leptin controls the body’s ‘fat thermostat’ and without it the mice quickly become obese. The scientists found that the obese mice had 50% fewer Bacteroidetes and 50% more Firmicutes in their bowel than their lean counterparts. In humans this was found to be the same. When obese people started to lose weight through low-fat and low-carbohydrate dieting, Bacteroidetes increased and in contrast Firmicutes decreased.

I find this a fascinating example of how little we understand the ways our gut microbiota influences our bodies and behaviour. Also, although our genes excert a great influence on our tendencies for obesity, other environmental factors like our bacterial composition have an equally important influence.

Notes of interest:
Can biosensors created to detect the levels of the hormone leptin in body indicate a potential obesiogenic future for that person?
Can the measurement of Bacteroidetes and Firmicutes be used to direct the future personal evolution of a person?
Will the products created in the p-evo clinics be required to react to genomic and environmental factors? If so, will there be a family of p-evo devices to predict certain gene and environmental factors?

Adipose Tissue (fat) has its own biological clock.

Biological Clock - source wikipedia

Circadian rhythms are ingrained in our lives; however, little attention has been paid to their metabolic consequences. It has been suggested that disruption of the circadian system may be related to expression of the metabolic syndrome (MetS) (1). Thus, shift work, sleep deprivation and exposure to bright light at night have been shown to be related to increased adiposity and prevalence of MetS (1,2).

Recent findings support the notion that rhythmic expression of circadian genes exists not only in the brain but in several other tissues (3,4). Along these lines, we have shown clock gene expression in human adipose tissue (AT) (5) and demonstrated that this expression was associated with different components of the MetS (5). An important question is whether this circadian clockwork can oscillate accurately and independently of the suprachiasmatic nucleus (SCN) in human AT and whether other genes are controlled by this process.

The objective of the present research was to analyze the circadian expression of the clock genes hPer2, hBmal1 and hCry1 in AT explants from morbid obese women from subcutaneous (SAT) and visceral (VAT) AT, in order to elucidate whether this circadian clockwork can oscillate accurately and independently of the SCN and if glucocorticoid metabolism-related genes such as that glucocorticoid receptor (hGr) and 11-hydroxysteroid dehydrogenase 1 (h11Hsd1) and the master transcription factor peroxisome proliferator activated receptor (hPPAR) are controlled by clock genes.

Full article: Obesity research journal – http://www.nature.com/oby/journal/vaop/ncurrent/full/oby2009164a.html

Circadian_rhythm_labeled - source wikipedia

Wikipedia on circadian clocks:

The primary circadian “clock” in mammals is located in the suprachiasmatic nucleus (or nuclei) (SCN), a pair of distinct groups of cells located in the hypothalamus. Destruction of the SCN results in the complete absence of a regular sleep/wake rhythm. The SCN receives information about illumination through the eyes. The retina of the eyes contains not only “classical” photoreceptors but also photoresponsive retinal ganglion cells. These cells, which contain a photo pigment called melanopsin, follow a pathway called the retinohypothalamic tract, leading to the SCN. If cells from the SCN are removed and cultured, they maintain their own rhythm in the absence of external cues.

It appears that the SCN takes the information on the lengths of the day and night from the retina, interprets it, and passes it on to the pineal gland, a tiny structure shaped like a pine cone and located on the epithalamus. In response the pineal secretes the hormone melatonin. Secretion of melatonin peaks at night and ebbs during the day and its presence provides information about night-length.

The circadian rhythms of humans can be entrained to slightly shorter and longer periods than the Earth’s 24 hours. Researchers at Harvard have recently shown that human subjects can at least be entrained to a 23.5-hour cycle and a 24.65-hour cycle (the latter being the natural solar day-night cycle on the planet Mars).^[13]

Determining the human circadian rhythm

The classic phase markers for measuring the timing of a mammal’s circadian rhythm are

• melatonin secretion by the pineal gland and
• core body temperature.

For temperature studies, people must remain awake but calm and semi-reclined in near darkness while their rectal temperatures are taken continuously. The average human adult’s temperature reaches its minimum at about 05:00 (5 a.m.), about two hours before habitual wake time, though variation is great among normal chronotypes.

Melatonin is absent from the system or undetectably low during daytime. Its onset in dim light, dim-light melatonin onset (DLMO), at about 21:00 (9 p.m.) can be measured in the blood or the saliva. Its major metabolite can also be measured in morning urine. Both DLMO and the midpoint (in time) of the presence of the hormone in the blood or saliva have been used as circadian markers.

However, newer research indicates that the melatonin offset may be the most reliable marker. Benloucif et al. in Chicago in 2005 found that melatonin phase markers were more stable and more highly correlated with the timing of sleep than the core temperature minimum. They found that both sleep offset and melatonin offset were more strongly correlated with the various phase markers than sleep onset. In addition, the declining phase of the melatonin levels was more reliable and stable than the termination of melatonin synthesis.^[14]

One method used for measuring melatonin offset is to analyze a sequence of urine samples throughout the morning for the presence of the melatonin metabolite 6-sulphatoxymelatonin (aMT6s). Laberge et al. in Quebec in 1997 used this method in a study which confirmed the frequently found delayed circadian phase in healthy adolescents.^[15]

Outside the “master clock”

More-or-less independent circadian rhythms are found in many organs and cells in the body outside the suprachiasmatic nuclei (SCN), the “master clock.” These clocks, called peripheral oscillators, are found in the esophagus, lung, liver, pancreas, spleen, thymus and the skin.^[16] Though oscillators in the skin respond to light, a systemic influence has not been proven so far.^[17][18] There is some evidence that also the olfactory bulb and prostate may experience oscillations when cultured, suggesting that also these structures may be weak oscillators.

Furthermore, liver cells, for example, appear to respond to feeding rather than to light. Cells from many parts of the body appear to have freerunning rhythms.

Disorders

There are many health problems associated with disturbances of the human circadian rhythm, such as seasonal affective disorder (SAD), delayed sleep phase syndrome (DSPS) and other circadian rhythm disorders.^[24] Circadian rhythms also play a part in the reticular activating system which is crucial for maintaining a state of consciousness. In addition, a reversal in the sleep-wake cycle may be a sign or complication of uremia,^[25] azotemia or acute renal failure.

Disruption

Disruption to rhythms usually has a negative effect. Many travelers have experienced the condition known as jet lag, with its associated symptoms of fatigue, disorientation and insomnia.

A number of other disorders, for example bipolar disorder and some sleep disorders, are associated with irregular or pathological functioning of circadian rhythms. Recent research suggests that circadian rhythm disturbances found in bipolar disorder are positively influenced by lithium‘s effect on clock genes.^[26]

Disruption to rhythms in the longer term is believed to have significant adverse health consequences on peripheral organs outside the brain, particularly in the development or exacerbation of cardiovascular disease [2] The suppression of melatonin production associated with the disruption of the circadian rhythm may increase the risk of developing cancer.^[27][28]

Fat as an Endocrine Organ

Obesity is a challenging health problem in Western societies. It is a risk factor for cardiovascular morbidity and mortality. Recent studies showed that adipose tissue is not only a passive energy store, but also an active endocrine organ, the secretions of which influence the function of many systems. It has been well known for decades that obesity influences the main ‘players’ of blood pressure regulation, in other words, the heart (increased cardiac output, cardiomyocyte hypertrophy), blood vessels (atherosclerotic changes, increased vascular resistance secondary to hypertrophy of vascular myocytes, increased vascular tone induced by sympathetic activity, abnormal paracrine/autocrine function of the endothelial cells), kidneys (sodium retention, activation of the renal renin-angiotensin system, development of obesity-related glomerulopathy), and the sympathetic nervous system (enhanced activity). In addition, obesity leads to endocrine, metabolic, haemostatic and haematological abnormalities.

• Endocrine: enhanced activity of the renin-angiotensin-system, hyperinsulinaemia with insulin resistance, diabetes mellitus type 2, hypercortisolaemia, resistance to natriuretic hormones.

• Metabolic: carbohydrate intolerance, increased synthesis of advanced glycated endproducts (AGE), increased plasma levels of free fatty acids, LDL cholesterol and small dense LDL, decreased HDL, hyperuricaemia.

• Haemostatic: increased blood clotting, increased plasma concentration of fibrinogen, plasminogen activator inhibitor (PAI-1) with reduced fibrinolytic activity.

• Haematological: polycythaemia mainly due to sleep apnoea, hypoxaemia and secondary increase of erythropoietin concentration.

As mentioned above, the adipose tissue is an important endocrine organ producing biologically active substances with local and/or systemic action. An incomplete list comprises PAI-1, transforming growth factor ß (TGF-ß), tissue factor (TF), complement factors (e.g. adipsin), adipocyte complement-related protein (Adipo-a), tumour necrosis factor-{alpha} (TNF-{alpha}), acylation stimulating protein (ASP), angiotensinogen, prostaglandin (PGI 2{alpha}), insulin-like growth factor-1 (IGF-1), macrophage inhibitory factor (MIF), sex hormones and glucocorticoids, angiotensin II, leptin, adiponectin and resistin (for review see [1,2]). Adipocytes also have receptors which respond to hormones, cytokines, growth factors and metabolites. The interaction between efferent signals (from adipocytes to other organs) and afferent signals (received by adipocytes) constitutes an elegant feedback system capable of adapting to the numerous challenges of energy metabolism. In this editorial we concentrate on nephrological aspects of some selected secretary products, in other words leptin, adiponectin, TNF-{alpha}, resistin and angiotensin II which are all involved in blood pressure regulation and/or target organ damage.

For full article visit: http://ndt.oxfordjournals.org/cgi/content/full/17/2/191

Reflections:
What new bio-sensors or synthetic biology devices can be created to detect/sense and feedback the presence of the hormones related to the endocrine system? How can the cyclic effect of excess adipose tissue and its negative effects on the endocrine system be intervened?

Teenagers

“No other species has teenagers. Even our closest relatives, the great apes, move smoothly from their juvenile to adult life phases. So why do humans spend an agonising decade or so skulking around in hoodies? Traditionally, the teenage years have been seen simply as a sort of reproductive apprenticeship, but a better understanding of adolescence had spawned some more interesting explanations.

David Bainbridge of the University of Cambridge, author of Teenagers: A natural history, says there are two big clues. The first is when adolescence evolved. Evidence from growth in the bones and teeth of fossilised hominins indicates that it emerged sometime between 800,000 and 300,000 years ago. This, he notes, pre-dates by a “fascinatingly short period” the great leap forward in human brain size, when our ancestors’ brains underwent the last big expansion to reach today’s size.

The second clue comes from neurobiology and brain imaging, which show that there is a wholesale reorganisation of hte brain during the teenage years. “The brain is roughly the same size at 20 as it is at 12, yet we can so so much more with it,” Bainbridge says.”

Douglas, Kate, 10 Mysteries of You, New Scientist, 8 August 2009, p.30-31

Reactions and Thoughts:
By using Puberty-Blockers can a sub category of the teenager be created to maximize on the reordering of the brain’s neurobiology and therefore to enhance our evolution – as well as having an impact on our species’ rate of population growth – with less people at the age of sexual maturity?

What new systems, objects, products and institutions will emerge to cater for the new teenager and prepare them for neurobiology re-wiring? What experiences will be created or simulated to add value to this re-wiring and evolution enhancement?

Words: ‘Peter-Pan’, ‘you are what you think’, ‘teenage kicks’, ‘old before their time’
Sources and notes of interest:
David Bainbridge, University of Cambridge and author of Teenagers: A natural history
Barry Bogin, Loughborough University (American Journal of Human Biology, vol 21, p567)

beebeard prototype

Beebeard prototype

beebeard

Beebeard

An old friend – Beebeard

Conceived during Obesity but has new underlying contexts of colony collapse.

Delay puberty

“Transsexual children as young as 12 should be given drugs to postpone puberty and make it easier for them to change sex at the age of 16 if they still want to.  That’s the suggestion of the controversial draft guidelines, the first of their kind, issued last week (13 December 2008) by the international Endocrine Society.

The guidelines state that transsexual children and young teens who have begun early puberty should be given puberty-blockers to avoid inevitable changes to their bodies, which they perceive as out of line with their true gender. In the worst cases, these changes can drive children to self-harm or even suicide.

The idea is to buy thinking time for young people so they can decide if they want to begin a sex change using hormones when they are older. Puberty-blockers would also make life easier when transsexuals become adults. Male-to-female transsexuals for example, will not have the deep voice, masculine bone structure and body hair associated with adult men.”

Geddes, Linda, Delay puberty in transsexual teens, New Scientist 13 December 2008, p.8-9

Reactions to delaying puberty:
Puberty-Blockers are a very immediate way of controling personal evolution. Issues arise with the age in which children make the decision to take the treatment – could they be used on a whim? For fashion? Or by ultimate pushy parents who want to buy time for their children to gain extra years of schooling for the best exam results? Alternatively perscribed by the state in the water supply to surpress reproduction in the under-classes (note to self – buy bottled water)?

Organisations and researchers to note:
International Endocrine Society
Henriette Delemarre-van de Waal, Leiden University (a clinic in Netherlands which has prescribed puberty-blockers to more than 70 under 16s)
Russell Viner, Institute of Child Health, London (experience of transsexual teens)
Marvin Belzer, Children’s Hospital, Los Angeles (treated several 12 and 13 year olds with puberty-blockers)
Peggy Cohen-Kettenis, Free University of Amsterdam Medical Center (helped write the guidelines)
Bernard Reed, trustee of the Gender Identity Research and Education Society in Ashtead, UK (hopes guidelines will encourage UK doctors to consider the option of early treatment).