Review article
Fat storage and the biology of energy expenditure

https://doi.org/10.1016/j.trsl.2009.05.003Get rights and content

Excessive adiposity results from an imbalance in energy homeostasis, whereby the consequences of excessive food intake are not balanced by increased energy expenditure. The increasing prevalence of excessive adiposity now involves more than 1 billion individuals worldwide. Of these, one half is obese and susceptible to comorbidities such as insulin resistance, type 2 diabetes, hyperlipidemia, and hypertension, which accelerate atherosclerosis. Lifestyle changes that have resulted largely in decreased physical activity now require a greater understanding of energy use that may allow better strategies for obesity control, because traditional methods of decreasing food intake and/or increasing exercise have not been successful without considerable behavioral counseling. This review focuses on the cell biology of white and brown fat tissue as well as on the central obesity that explains the comorbidities of the metabolic syndrome. Recent advances regarding the roles of central and autonomic nervous system regulation involved in fat remodeling are discussed, including the hypothalamic regulation of food intake and intestinal modulation, which affects satiety and peripheral energy expenditure. Finally, the new knowledge of cellular transcription factor regulation of energy expenditure is explained, whereby genes regulate mitochondriogenesis within adipocytes, liver, and muscle for both coupled and uncoupled oxidative phosphorylation-induced energy and heat expenditure, respectively. Newly discovered agonists of these transcription factors may now be realized that enhance energy expenditure. Strategies that combine such pharmacotherapies with lifestyle changes including enhanced physical activity and proper dietary intake may then provide the deterrents to excessive adiposity and its comorbidities, which now threaten human longevity.

Section snippets

Adipogenesis, BAT and WAT Function, and the Pathophysiology of Visceral Fat Depots

Although adipocytes originate from mesodermal tissue, new knowledge reveals how specific transcription factors control the DNA transcription of downstream gene targets in mesenchymal stem cells for preadipocyte differentiation into mature adipocytes.7 This results in differentiation into WAT for fat storage of triacylglycerol or BAT for production of heat, but both tissues contribute to energy expenditure.8 A mutation in serine phosphorylation within the transcription factor peroxisome

Fat Remodeling and Regulation of Energy Homeostasis by Central and ANS Regulation

Fat remodeling is an essential dynamic process that ensures adequate body fat mass and energy homeostasis without excessive weight gain or loss. Increased appetite and food intake promotes a positive energy balance with weight gain, whereas satiety limits food consumption that favors negative energy balance and weight loss through hypothalamic neuropeptide regulation of appetite and satiety.20 CNS and ANS regulation of energy expenditure are integrated to achieve a balanced energy homeostasis

Intestinal Hormone Modulation of Energy Use

The ANS provides input to and from the gastrointestinal tract through parasympathetic vagal innervation from the nucleus tractus solitarious and the SNS from the spinal cord intermediolateral cell column. Furthermore, the roles of central hypothalamic neuropeptide regulation of food intake are complemented by intestinal hormonal modulation that involves integration of the CNS and ANS. This explains how normal total body fat mass can be regulated by fat remodeling based on the CNS hypothalamic

The Molecular Biology of Energy Use within Muscle, Liver, and Fat Tissues by Nuclear Hormone Receptors and their Coactivators

The transcription factor family of PPARs first discovered in the early 1990s include the following 3 isoforms: α, γ, and Δ, which, along with the more recently discovered PPAR gamma coactivator-1α (ie, PGC-1α), control the downstream gene expression that regulates key sites of energy use in muscle, liver, and fat.41

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