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References – Adipose Tissue

Summary of articles:

Adipose tissue serves two primary functions

  1. As a storage depot for excess energy. It provides a safe location for energy to be stored away and provides a pool of energy that can be used during times of fasting.
  2. As a key component of the endocrine system, playing a crucial role in the signaling network that allows the body to maintain metabolic homeostasis.

Without well-functioning adipose tissue:

  1. Excess energy cannot be stored away in a safe location, and instead will find its way to more dangerous locations.
  2. Metabolic signaling cannot be performed optimally, leading the body to a systemic state of metabolic dysregulation and dysfunction.

See the following references:

Sethi, J. K., & Vidal-puig, A. J. (2007). Adipose tissue function and plasticity orchestrate nutritional adaptation. 48. https://doi.org/10.1194/jlr.R700005-JLR200

White adipose tissue serves two primary functions:

  1. As a storage depot for surplus energy as triglycerides, which can be released in the form of free fatty acids.
  2. As an endocrine organ, being involved as a primary communicator of the energetic status of the body. The primary signal involved in communicating the energetic fullness of the adipose tissue is leptin, which goes on to play a role in hunger signaling.

Brown Adipose Tissue “stores triglycerides in multilocular adipocytes as quick-access fuel for heat production through mitochondrial “uncoupling” of oxidative phosphorylation of FFA.”

Adipose tissue serves an important role as a safe site of energy storage: “the ablation of adipose depots exacerbates peripheral insulin resistance through hyperlipidemia-induced lipotoxicity and is reminiscent of the metabolic abnormalities associated with lipodystrophic disorders in lean individuals.” This is to say, removing adipose tissue leads to hyperlipidemia and the pathophysiologic conditions that go along with it (e.g. insulin resistance).

Adipose tissue plays a role in systemic glucose homeostasis. Adipose tissue is one of the few organs that has the ability to convert large amounts of gluocse into fat (the liver is the other major organ with this ability). Without this ability, the body is at risk for insulin resistance and metabolic dysfunction, as was demonstrated by Glut4 knockout.

When tissue expansion becomes limited as it reaches a certain threshold, energy must be driven elsewhere: “What happens when the adipose tissue expandability becomes a limiting factor and nutrients cannot be stored safely in the adipocyte? These nutrients are redirected toward other organs, such as muscle, liver, heart, or pancreas. These tissues are not designed to store large amounts of lipids and therefore are more susceptible to the toxic effects of excess fat accumulation.”

Tandon, P., Wafer, R., & Minchin, J. E. N. (2018). Adipose morphology and metabolic disease. https://doi.org/10.1242/jeb.164970

From the abstract: “Adipose tissue with fewer but larger adipocytes is said to have a ‘hypertrophic’ morphology, whereas adipose with many adipocytes of a smaller size is said to have a ‘hyperplastic’ morphology. Hypertrophic adipose morphology is positively associated with insulin resistance, diabetes and cardiovascular disease. By contrast, hyperplastic morphology is associated with improved metabolic  parameters. These phenotypic associations suggest that adipose morphology influences risk of cardiometabolic disease.”

Brief Summary: The morphology of adipose tissue can be broken up into two categories based on its ability of the adipocyte to expand and multiply. Whether these adipocytes have the ability to multiply largely determines the development of insulin resistance. The cellular mechanisms that determine how an individual’s adipocytes  expand are largely undetermined, but include regulation by the outer membrane of the cell and osmolarity sensing. The extent to which genetic factors and environmental factors influence these is largely undetermined (according to this particular paper; This is examined in Moreno-Indias et. al (2015); see below).

Key Points: Adipose tissue is not a passive storage depot that responds similarly across individuals. Based on the individual’s adipose tissue morphology, the individual may be prone to developing insulin resistance and downstream disease, including diabetes and cardiovascular disease.

Moreno-Indias, I., & Tinahones, F. J. (2015). Impaired adipose tissue expandability and lipogenic capacities as ones of the main causes of metabolic disorders. Journal of Diabetes Research, 2015. https://doi.org/10.1155/2015/970375

Key factors determining adipose tissue expansion and metabolic dysfunction (note, below I mention just 1 factor; see the paper for the full list)

  1. PPARG is a nuclear receptor involved in adipogenesis and lipogenesis; “The activation of PPAR leads to adipocyte differentiation and fatty acid storage, whilst it represses genes that induce lipolysis and the release of free fatty acids (FFA) in adipocytes [reference]. Failure in the metabolism of this molecule leads to dysregulation in the optimal lipid storage and mobilization, the main problem of obesity”
  2. “…subjects with IR and obesity have a reduced PPARG expression, both fasting and postpandrially [references]. Morbidly obese patients and patients with diabetes have a lower expression of PPARG2 mRNA in comparison with morbidly obese insulin sensitive patients, both in VAT and muscle [reference]. This is closely associated with the storage capacity in adipose and muscle tissues, with the mismatch between energy surplus and storage capacity in adipose tissue and muscle tissues possibly being an important factor linking obesity and IR [reference].”

Key Points:

“Adipose tissue … can be considered another vital organ, mainly due to its endocrine properties. Adipocytes are the main units in adipose tissue, and this tissue is considered to control the whole body metabolism, so dysregulation can have huge consequences for health. Adi- pose tissue dysfunction is thought to be themajor factor leading to whole body IR [reference]. Beyond expandability of adipose tissue, the essential pathological changes of adipose tissue affect whole body energy homeostasis and integrity.”

“the large interindividual variability observed in adipocyte size at a given adiposity level suggests that the tendency to fat cell hypertrophy in each fat compartment may differ among individuals [reference].”

My commentary: Adipose tissue is tightly regulated by a number of factors, primary among them being PPARG. The functionality of these factors vary among individuals, and depending on this individual variability, each individual will be uniquely susceptible to the ability to store fat, and in turn, the development of metabolic dysfunction and modern disease.

F. J. Ortega,D.Mayas,J.M.Moreno-Navarreteetal.,“The gene expression of the main lipogenic enzymes is downregulated in visceral adipose tissue of obese subjects,” Obesity,vol.18, no.1, pp.13–20,2010.

This title says it all: The gene expression of the main lipogenic enzymes is downregulated in visceral adipose tissue of obese subjects.

Key Point: Adipose tissue expansion –> decreased ability to take in more energy for storage

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