Circadian rhythm in the pancreas —

Circadian clocks have profound effects on metabolism and behaviour , in plants and mammals.

In 1972, a study demonstrated that within the brain hypothalamus, the suprachiasmatic nucleus, which is close to the optic nerves, is required for daily rhythms in animal behaviour. The suprachias¬matic nucleus receives light signals through the optic nerves, and so uses daylight cues to set the clock time and to couple light-dark transi¬tions to behavioural outputs.

Subsequent genetic studies identified several genes that mediate rhythmic behaviour.

The mammalian circadian clock is a molecular oscillator based on a negative feedback loop in which the transcription factors CLOCK (or the related protein NPAS2) and BMALl work together to drive the expres¬sion of many genes, including the period (PERl, PER2 and PER3) and the cryptochrome (CRYl and CRY2) proteins.

Now it is clear that clocks outside the suprachiasrnatic nucleus have physiological roles?

First, expression of enzymes, transporters and receptors that regulate metabolism fluctuate robustly throughout the day.

Second circadian clocks outside the suprachiasmatic nucleus are adjusted on the basis of feeding time rather than the light-dark schedule For example, the cellular energy sensor AMPK controls the stability of cryptochromes and may contribute to nutrient entrainment of the clock in the liver.

Marcheva et al. have shown that the mouse pancreas also has a functional circadian clock, with individual pancreatic islets having clock function even when outside their normal tissue environment. The islet clock seems to consist of the same components as other mammalian circadian clocks, and drives rhythmic expression of genes involved in insulin sensing, glucose sensing, and islet growth and development. These clocks are therefore crucial for the specific metabolic needs and functions of islet cells .

Lamia and Evans 2010 Tick, tock , a ß-cell clock Nature vol 466, 571-2

Marcheva et al 2010 Disruption of the clock components CLOCK and BMAL1 leads to hyper-insulinaemia and diabetes Nature vol 466 627-631

Thermodynamics Made Easy —

Peter Atkins has written a non mathematical book on thermodynamics.

To my mind there are three elements to nutrition.

1. What goes into the system ( food)

2. How the food is metabolised ( metabolism and thermodynamic)

3. What happens to the metabolic process e.g. growth , exercise etc

Whilst much attention is given to 1 and to an extent 3 few in Nutrition with noteworthy heroes cope with 2

The reason is simple we who are attracted to nutrition are not attracted to the subject because of its mathematical content. Quite the converse. Most of our maths is restricted to counting calories.

But thermodynamics are to be neglected at our peril

The underlying problems will be resolved by an understanding of the thermodynamics of the obese system.

Or maybe obesity is some form of infection rather as duodenal ulcers turned out to be not due primarily to acid but the Helicobacter bacteria.

The book which is well recommended is

Four laws that drive the universe Peter Atkins Oxford University Press

Thermogenisis and Obesity —

Adaptive reduction in thermogenesis and resistance to lose fat in obese men

Adaptive thermogenesis is defined as a greater than predicted change in energy expenditure in response to changes in energy balance. This issue is particularly relevant in the context of a weight-reducing programme in which diminished thermogenesis can be sufficient to compensate for a prescribed decrease in daily energy intake.

In the pilot study,described in this paper Tremblay and Chaput in British Journal of Nutrition investigated the adaptive reduction in thermogenesis in resting state that appears to favour resistance to further weight loss.

Eight obese men (mean BMI: 33•4kglm2, mean age: 38 years) participated in this repeated-measures, within-subject, clinical intervention. They were subjected to a weight-loss programme that consisted of a supervised diet (- 2930 kJ/d) and exercise clinical intervention.

The phases investigated were as follows: (i) baseline, (ii) after 5 (SE I) kg loss of body weight (phase 1), (iii) after 10 (SE 1) kg weight loss (phase 2) and (iv) at resistance to further weight loss (plateau).

At each phase of the weight-reducing programme, body weight and composition as well as Resting Metabolic Rate were measured. A regression equation was established in a control population of the same age to predict Resting Metabolic Rate obese men at each phase of the weight-loss programme. We observed that body weight and Fat Mass were significantly reduced (P<0•05), while fat-free mass remained unchanged throughout the programme.

In phase 1, measured Resting Metabolic Rate had fallen by 418kJ/d, more than predicted (P<0•05), and this difference reached 706kJ/d at plateau (P<0•05 v. phase 1). A positive associ¬ation (r 0•64, P< 0•05) was observed between the reduction in thermogenesis and the degree of Fat Mass depletion at plateau. The adaptive reduction in thermogenesis at plateau was substantial and represented 30•9 % of the compensation in energy balance that led to resistance to further lose body weight.

They suggest that these results show that adaptive reduction in thermogenesis may contribute to the occurrence of resistance to lose fat in obese men subjected to a weight-reducing programme.

Tremblay and Chaput 2009 Adaptive reduction in thermogenesis and resistance to lose fat in obese men Brit J Nutrition vol 101 488-492