Energy Balance, Obesity and Type‐2 Diabetes

Abstract

Energy balance is determined by caloric intake versus caloric expenditure. Complex control systems promote energy storage (primarily as adipose tissue fat) during periods of food surplus and mobilization of energy stores when food is scarce. These regulatory systems operate both locally within cells and between different body tissues and are mediated by circulating hormones and direct neural connection from the central nervous system to peripheral tissues. In modern society where lifestyles have shifted towards the excessive consumption of palatable ‘high energy’ foods and a sedentary life, these control mechanisms can be circumvented and in so doing lead to obesity and its pathological consequences. Prominent among these consequences are insulin resistance, i.e. the inability of cells to respond normally to insulin, and Type‐2 diabetes. Approximately 30% of the inhabitants of the United States meet the criteria for obesity.

Key concepts

  • Animals possess complex control systems with which to regulate energy storage and expenditure.

  • The concept of energy balance.

  • How is blood glucose level regulated?

  • How do changes in blood glucose level alter the secretion of hormones that regulate energy metabolism?

  • What are the major physiological fuels that provide energy for different cell types and how do changes in hormone level affect fuel production and utilization?

  • Nature of interplay between tissues/organs through the production and utilization of circulating physiological fuels.

  • What is insulin resistance and what are its consequences?

  • What constitutes the obese state and how does obesity lead to insulin resistance and Type‐2 diabetes?

  • how adipocytes develop from stem cells and the consequences of adipocyte hyperplasia.

  • How does persistent obesity lead to failure of the insulin‐secreting pancreatic β‐cell and the diabetic state?

Keywords: fat; insulin; glucagons; body mass index; β‐cell

Figure 1.

Effect of nutritional state (a and b) and Type‐2 diabetes (c) on tissue fuel reserves and circulating physiological fuels. (a) When fed an energy‐rich diet after fasting dietary CHO is first used to restore blood glucose level and replete liver glycogen reserves. Next excess dietary CHO and fat are diverted into triglyceride (fat) synthesis in the liver, which is transported to adipose tissue as very low‐density lipoprotein to adipose tissue where fatty acids are released, resynthesized into triglyceride and stored. Under these circumstances the blood levels of insulin, glucagon and epinephrine change in the directions of the vertical arrows. (b) In the fasted state (food deprivation) liver glycogen is converted into glucose and is released into the blood stream. When this glycogen reserve is depleted, protein from tissues (primarily skeletal muscle) is mobilized as amino acids. The amino acids are transported in the blood to the liver where they are converted via gluconeogenesis into glucose, which is released into the blood stream. Concurrently, adipose tissue triglyceride is mobilized as fatty acids and released into the blood stream. The fatty acids are both used directly as fuels for many tissues (liver and muscle, but not brain) and also are taken up by the liver and converted into ketones (β‐hydoxybutyrate and acetoacetate). The ketones are released into the blood stream and utilized as an alternative fuel for the brain (CNS neurons) and muscle. (c) In the pathological Type‐2 diabetic state most cells become insulin resistant, which leads to hyperglycaemia and hyperlipidaemia (elevated blood fatty acid level) compounded by hyperinsulinaemia (see text for an explanation). The boxed numbers Cahill, and Wolfgang and Lane, indicate the sequence in which the transition occurs.

Figure 2.

Glucose‐activated insulin secretion by the pancreatic β‐cell. When the blood glucose level rises the sequence of events lead to increased insulin (solid circles) secretion (see text for details). K+ and Ca2+ refer to the potassium and calcium ions, respectively.

Figure 3.

Regulation of hepatic energy metabolism in the ‘fed’ state. Under the physiological conditions described in Figure a the pathways illustrated by the broad arrows dominate over those represented by thin arrows. The control features shown by + and − illustrate the basis for the changes in flux through the pathways. Changes in the regulatory factors that cause these changes are described in the text. TCA, tricarboxylic cycle; Ac‐CoA, acetyl‐CoA; VLDL, very low‐density lipoprotein; PEP, phosphoenolpyruvate; cAMP, cyclicAMP.

Figure 4.

Regulation of hepatic energy metabolism in the ‘food deprived’ (fated) state. Under the physiological conditions described in Figure b the pathways illustrated by the broad arrows dominate over those represented by thin arrows. The control features shown by + and − illustrate the basis for the changes in flux through the pathways. Changes in the regulatory factors that cause these changes are described in the text. Abbreviations are as in the legend to Figure and 5′3‐AMPK refers to 5′‐AMP kinase.

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References

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Further Reading

Ashcroft FM (2007) ATP‐sensitive potassium channelopathies: focus on insulin secretion. Journal of Clinical Investigation 115: 2047–2058.

Muoio DM and Newgard CB (2008) Mechanisms of disease: molecular and metabolic mechanisms of insulin resistance and beta‐cell failure in type 2 diabetes. Nature Reviews: Molecular Cell Biology 9: 193–205.

Owen OE, Kalhan SC and Hanson RW (2002) The key role of anaplerosis and cataplerosis for citric acid cycle function. Journal of Biological Chemistry 277: 30409–30412.

Schwartz MW and Porte D Jr (2005) Diabetes, obesity, and the brain. Science 307: 375–379.

Wahren J and Ekberg K (2007) Splanchnic regulation of glucose production. Annual Reviews of Nutrition 27: 329–345.

Winder WW and Hardie DG (1999) AMP‐activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. American Journal of Physiology 277(1 part1): E1–E10.

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Daniel Lane, M(Mar 2009) Energy Balance, Obesity and Type‐2 Diabetes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021317]