Understanding Energy: Fat and Protein Storage
The first piece in “Understanding Energy” examined how dietary carbohydrates are metabolized and stored.
This follow-up piece will address the metabolism of dietary fat and protein.
Fat
Dietary fat is mainly composed of triglycerides and phospholipids (the main component of plant and animal cell walls). A triglyceride contains three (hence, tri) fatty acids linked to a backbone called glycerol. Bile and enzymes in the mouth, stomach, and small intestine break down triglycerides into monoglycerides and fatty acids.
Monoglycerides are used to re-form triglycerides for transport in chylomicrons (discussed more below)
Fatty acids are categorized based on the amount of carbon atoms in their molecular chain (short-, medium-, or long-chain) and the types of chemical bonds present
Short-chain fatty acids (SCFAs) contain two to four carbons.
The primary source of SCFAs is the fermentation of dietary fiber, a form of carbohydrate, by the microbiome in the small intestine.
Medium-chain fatty acids contain six to twelve carbons.
Long-chain fatty acids contain more than fourteen carbons and are more abundant in animal- and plant-based foods compared to short-chain and medium-chain fatty acids.
Fatty acids are considered saturated when only single chemical bonds link neighboring carbons
High saturated fat intake is often linked to heart disease
Fatty acids are considered unsaturated when at least one double bond links neighboring carbons within the fatty acid chain
Monounsaturated: just one double bond is present
Polyunsaturated: multiple double bonds are present
Omega-3 and omega-6 fatty acids are types of essential polyunsaturated fats important in regulating inflammatory processes. The “omega” refers to the position of the final double bond in the carbon chain.
Omega-3 fatty acids are further subdivided as ALA, EPA, and DHA based on the total amount of carbons.
After initial enzymatic metabolism, fatty acids are absorbed by the small intestine.
Short-chain and medium-chain fatty acids are transported directly to the liver where they are bound to albumin, a protein carrier, and released into the blood
Long-chain fatty acids are re-converted into triglycerides by cells in the lining of the small intestine using monoglycerides as a backbone.
These re-formed triglycerides are carried with dietary cholesterol by vesicles called chylomicrons. Chylomicrons first enter the lymphatic system and then join the blood.
From the blood, chylomicrons and albumin-bound fatty acids are delivered to cells throughout the body.
Triglycerides within chylomicrons are broken down by enzymes into glycerol and fatty acids.
Glycerol enters glycolysis to directly form ATP or enters gluconeogenesis to form glucose.
Fatty acids are metabolized in a process called beta oxidation to form electron carriers for oxidative phosphorylation (the oxygen-dependent form of ATP creation) in mitochondria.
Albumin-bound fatty acids follow the same fate.
Once immediate energy needs are met, excess lipids are converted into storage forms.
Similar to carbohydrate metabolism, excess glucose derived from glycerol is stored as glycogen in the liver and skeletal muscle. Once the liver and muscle are saturated with glycogen, leftover glucose is converted into triglycerides by the liver and adipose tissue using excess fatty acids.
Under normal conditions, the liver stores few triglycerides and mainly releases its cache into the blood attached to a carrier molecule called VLDL (very low-density lipoprotein) to be delivered to peripheral cells.
Subcutaneous adipose tissue is the primary sink for excess triglycerides. As described below, when subcutaneous stores run out of space, lipids in the bloodstream search for another home and find one in visceral adipose tissue.
Gaining Fat: a Housing Story
To review, our body responds to a surplus of energy (i.e., caloric intake exceeds energy expenditure) by storing excess blood glucose as glycogen in liver and muscle. Once these stores are maximized, leftover glucose is converted into triglycerides, which are mainly stored in adipose tissue. Existing adipose cells expand their lipid content (hypertrophy) and new adipose cells are generated (hyperplasia).
An anthropomorphized example might be helpful in understanding these processes:
We can imagine subcutaneous adipose cells as apartments, triglycerides as renters, and visceral adipose cells as unconventional housing.
Because of good weather or an excellent food scene, a lot of new people move to town (an energy surplus). Vacant apartments quickly fill up with renters (hypertrophy).
In the body, hypertrophy of existing subcutaneous adipose tissue is likely the major driver of fat storage. This process is precipitated by an acute, transient inflammatory response.
Some building staff might misinform potential tenants there is no vacancy in existing apartments, leaving those renters to seek accommodation in unconventional places— say, couch-surfing or a long-term AirBnB.
Lack of a local inflammatory response prevents hypertrophy of subcutaneous adipose, promoting lipid deposition in visceral stores.
If there is consistent population growth (a sustained energy surplus), existing apartments will ultimately fill up and not be able to accommodate additional tenants. Enterprising minds may be alerted to this business opportunity and work to build new apartments (hyperplasia).
In the body, an additional local and systemic inflammatory program may be triggered that prompts the generation of new subcutaneous adipose tissue (hyperplasia) once existing subcutaneous fat reaches its limit for lipid accumulation.
Despite demand, building new apartments is sometimes impossible due to financing issues, an insufficient workforce, and zoning regulations, leading renters to again seek out unconventional housing.
When hyperplasia cannot occur, inflammatory signals might be prolonged, leading to hypertrophy of existing visceral adipose tissue.
Some evidence suggests the absolute number of adipose cells might be fixed based on body mass during childhood and adolescence, limiting later hyperplastic potential.
(While illustrative, this metaphor is not intended to trivialize the experience of people who aren’t able to find housing.)
Taken together, the growth of visceral adipose tissue depends on dysfunction of subcutaneous fat as a result of a consistent energy surplus.
An upcoming piece argues that the focus of public health should shift from BMI to visceral fat and describes strategies to reduce visceral fat burden.
Proteins
In comparison to the metabolism of dietary carbohydrates and fat, protein break-down is rather anodyne.
Proteins are metabolized into their constituent amino acids by enzymes in the stomach and small intestine. These amino acids are utilized to build proteins in skeletal muscle in a process called muscle protein synthesis (MPS) as well as form vital structures and molecules in all cells in the body.
Once protein synthesis has been saturated, excess amino acids are broken down primarily by the liver into:
Pyruvate, which enters the Krebs cycle to form electron carriers for oxidative phosphorylation or reforms glucose
Acetyl-CoA, which also enters the Krebs cycle or forms fatty acids.
During times of starvation, acetyl-CoA can also be converted to ketone bodies, a form of energy utilized mainly by the brain, heart, and skeletal muscle.
While energy requirements may still be met despite restricting intake of dietary carbohydrates or fats, there is little value in limiting protein consumption.
(While there is some evidence that restricting protein intake may improve metabolic health and extend lifespan, the risk of malnutrition, sarcopenia, and frailty considerably limit this approach.)
Sufficient dietary protein consumption is a biological imperative to fuel protein synthesis. In How Much Protein Do We Really Need?, I argue that the optimal protein intake is 0.73 to 1 gram of protein per pound of body weight for healthy active adults, about twice the FDA recommendation.
