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Body Fat And Metabolic Health

Feature Article Body Fat And Metabolic Health
SAT, 06 MAY 2023

ADIPOSE TISSSUES (BODY FATs) AND HEALTH.
Microscopically, body fats consist of the adipocytes, (the cells specialized in handling fats), nerve cells, blood vessels, white blood cells (WBCs) and the extracellular matrix.

Body fats have traditionally been classified as white and brown fats.

The most abundant body fat is the White body fat.
White body fat is found in every area of the body. 80% of the white body fat is found under the skin (subcutaneous fat where it acts as a thermal insulator), the rest of the white body fat is seen around the internal organs (visceral fat) where it acts as cushion for the internal organs.

Brown body fat is mainly seen above the collar bones, (in the neck), the underarms, and along the backbone (paravertebral region) The elderly populations have much lower amount of brown fats.

In white body fats, each adipocyte consists of a single large lipid droplet of triglyceride (the storage form of fat), and scanty mitochondria. White body fats store and release fats based on the energy demands of the body.

In brown body fats, the adipocytes consist of many fat droplets, and many mitochondria.

Brown body fats have dense capillary networks that supply adipocytes with oxygen and nutrients (glucose, fatty acids, amino acids) for oxidation, and help to distribute heat efficiently to the rest of the body.

Mitochondria are cellular organelles that convert food to ATP (cellular energy), CO2 and H20 he Mitochondrial enzyme, Cytochrome oxidase, has iron-containing-heme as cofactor. Brown adipocytes are packed with iron-rich mitochondria, hence their brown color.

Beige Body Fat.
A third type of body fat is known as beige body fat. Beige adipocytes are brown-like adipocytes that lie dormant in white adipose tissues. Beige adipocytes appear morphologically white but have beige adipocyte lineage.

When stimulated the beige adipocytes assume the characteristics of brown adipocytes. Stimulation changes their internal architecture: the stimulated adipocytes accumulate more mitochondria, and more lipid droplets.

The beige adipocytes return to their dormant state (white adipocytes), when the stimulus is removed.

Among the stimulants are:
. Exposure to cold weather.
. Sympathetic/noradrenaline stimulation.
. BDNF production in the hypothalamus.
. Exercise. (Exercise induced cytokines (Irisin and Meterorin-like) and exercise induced myokine, IL-6 activate beige adipocyte development).

. Diet (chili red pepper, catechins in green tea and cocoa, fish oils)

. Pre-and probiotics
. Plants-based bio actives like curcumin in turmeric

The health benefits of BEIGE/BROWN FAT
Brown fats act as metabolic sink for excess nutrients.

Excess glucose, fatty acids and the branched chain amino acids are utilized by brown fats for heat generation.

Brown fats oxidize branched chain amino acids during cold exposure.

High levels of branched chain amino acids in the plasma activate the mTOR1 enzymatic pathways. mTOR1 induces insulin receptor substrate (IRS-1) degradation. This impairs insulin signaling and results in insulin resistance and other metabolic disorders.

Brown fat reduces insulin resistance through the utilization of branched chain amino acids.

Brown fats therefore protects us against weight gain and metabolic dysfunction

Brown/beige fat increases energy expenditure.
BROWN FAT AND WEIGHT LOSS.
Certain cancers release proteins that promote beige adipocyte biogenesis and hypermetabolism. For example, parathyroid hormone-related protein (PTHrP) is released from Lewis lung carcinoma. PTHrP promotes beige adipocyte biogenesis. High levels of serum PTHrP are associated with cachexia.

WHITE BODY FAT.
In addition to being a reservoir of triglycerides (the storage form of fat), body fats act as endocrine organs that regulate energy expenditure, appetite, reproduction, inflammation, and immunity.

White body fat produces multiple hormones that are associated with metabolic syndrome.

White body fats receive hormonal input from insulin, growth hormone, cortisol and epinephrine.

Excessive amounts of visceral fat are associated with diabetes and heart diseases.

Visceral fats secrete inflammatory cytokines into the blood stream. This causes chronic low-grade metabolic inflammation. Systemic Chronic inflammation is associated with diabetes, certain cancers, atherosclerosis and heart diseases.

THE ROLE OF FAT TISSUE MACROPHAGES IN METABOLIC DISEASES.

Body fats contain white blood cells including B-cells, T-cells, and Neutrophils. However, the most abundant white blood cells (WBCs/immune cells) in body fats are the monocytes/tissue macrophages.

It is the release of cytokines from activated macrophages that affect our metabolic health.

Depending on what triggers their activation, macrophages can be broadly categorized as having either M1 macrophage (proinflammatory) or M2 macrophage (anti-inflammatory) phenotypes.

M1 macrophages activations trigger the production of pro-inflammatory cytokines (TNF, 1L-6,) and mediates obesity-induced insulin resistance and type 2 diabetes.

M 2 activation triggers the release of IL-10 (an anti-inflammatory factor) and other chemokines involved in tissue repair, angiogenesis and oxidative metabolism.

In obese people, there is a shift in frequency from M2 macrophages (anti-inflammatory) to M1 macrophages (pro-inflammatory) and this correlates with insulin resistance.

In the presence of excess nutrients, fat cells replicate and enlarge to outstrip their vascular supply. Tissue ischemia and necrosis set in.

This attracts M1 macrophages.
M1macrophages produce: IL-6, TNF-alpha.
IL-6 from adipose tissues trigger liver cells to produce and secrete C- reactive protein, and fibrinogen.

IL-6 triggers the bone marrow to release WBCs and platelets

1L-6 activates vascular endothelium and procoagulant factors.

Indeed, visceral fat strongly correlates with higher risk for diabetes and cardiovascular diseases.

Adiponectin
Adiponectin is exclusively secreted from body fats and is the most abundant adipokine (plasma levels of 5-10 mcg/ml).

Adiponectin modulates the proliferation of MI and M2 macrophages.

Whereas Adiponectin promotes M2 macrophage proliferation, it suppresses proliferation of M1 at the myelomonocytic progenitor stage and inhibits mature M1 macrophage activation.

This accounts for the anti-inflammatory properties of adiponectin.

Catecholamines act on the beta2-adrenergic receptors on macrophages to promote anti-inflammatory (M2) macrophage function; this results in reduced inflammation.

Adiponectin is an adipocyte derived hormones that have antidiabetic, anti-inflammatory and anti-atherogenic effects. Adiponectin protects vascular endothelium by increasing nitric oxide production, locally.

Nitric oxide does several things: Protects against endothelial dysfunction, inhibits plaque initiation, Inhibits thrombosis.

In the liver, adiponectin: Increases insulin sensitivity, reduces the uptake of FFAs for adipogenesis, decreases gluconeogenesis, increase beta oxidation by regulating lipid metabolism genes in adipocytes

In the brain adiponectin: Regulates weight gain and Increases energy expenditure.

OBESITY AND ADIPONECTIN
Obesity predisposes to a pro-inflammatory state via increased inflammatory mediators IL-6 and TNF-α, and reduced levels of adiponectin, which has totally anti-inflammatory function.

TNF-α is overexpressed in the overweight state.

IL-6 is linked more to the obese state.
Both IL-6 and TNF-alpha inhibit and reduce adiponectin synthesis and secretion.

Low levels of adiponectin promote endothelial dysfunction and loss of cardio-protection.

A fall in adiponectin levels below 4.0mcg/dl (hypoadiponectinemia) is associated with the features of metabolic syndrome: Elevated FBG, Elevated TG, Low HDL-C, Reduced LDL-C particle size, Elevated BP.

Low levels of adiponectin increase the markers of systemic inflammation and an overall increased risk for metabolic syndrome.

The complications of obesity-induced hypoadiponectinemia are atherosclerosis, hypertension, alteration of metabolic markers, and heart diseases.

Leptin
Obesity is associated with elevated levels of circulating leptins. Leptin levels signify energy sufficiency; leptin levels rapidly decline with calorie restriction.

TNF-Alpha
. TNF-Alpha levels are increased in obesity; the levels correlate with adiposity and insulin resistance. In liver cells, TNF-Alpha activates genes involved with cholesterol and fats synthesis, and suppresses genes involved with glucose, and fats burning.

IL-6
Circulating levels of Il-6 correlate positively with obesity, impaired glucose tolerance and insulin resistance. When administered peripherally, IL-6 induces hyperlipidemia, hyperglycemia and insulin resistance in humans.

Proteins of the renin-angiotensin system
One of the reasons why obesity is associated with hypertension is that adipocytes secrete proteins and enzymes that can locally, generate Angiotensin II.

Angiotensin II (ATII) is the most potent constrictor of blood vessels. ATII causes sodium and water retention, and aldosterone release from the adrenal glands. All these contribute to the development of hypertension.

The plasma levels of most adipokines decrease with fasting and rise with refeeding.

What Next?
Brown body fats act as metabolic sink for excess glucose, lipids and amino acids. Thus, brown and beige fats by raising the basal metabolic rate, help to prevent obesity, diabetes and atherosclerosis.

Lifestyle and dietary changes that promote brown fat generation include:

Regular Exercise. Exercise promotes BDNF production, and norepinephrine release, both of which promote brown fat production. Walk fast for at least 30 minutes every morning (before meals) and evening (after meals).

Exercise a lot outside, especially in cold weather situations.

Include chili red pepper, and whole food plant-based recipes in our meal menus.

Drink flavonoid-rich teas like green tea, cocoa drinks daily

Add spices like turmeric and black pepper to your meals.

Since the plasma levels of adipokines decrease with fasting and increase with refeeding, and being overweight and obese favor MI-macrophage (proinflammatory),

It is prudent to practice intermittent fasting and time-restricted feeding (TRF). In TRF you eat all your meals within an 8-hour period, usually from 8am to 4pm, and fast for the next 16 hours every day. This promotes autophagy. Autophagy allows the cells in our body to do their own house-cleaning, promotes energy balance, get rid of pathogens and abnormal cellular structures and repair damaged DNAs. Autophagy thus helps to keep our body cells heathy and helps us to stay young.

By staying trim and healthy, many chronic and metabolic diseases can be avoided and controlled.

Alex Sarkodie MD
Alex Sarkodie MD, © 2023

Alex Sarkodie,MBChB has over 30 years experience in the field of MedicineColumn: Alex Sarkodie MD

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