[MUSIC] Hello, everyone, welcome back to my Coursera class, Biochemical Principles of Energy Metabolism. We finished the first half of course. I mean, we spent four weeks in the past. And we reviewed about basic principles of metabolic processes. In particular, I believe I gave you a very clear foundation on the biochemical processes of how carbohydrates can be oxidized into usable energy. I mean, ATP molecules. So for this week, I'm going to, Deliver the basic principles of fat metabolism. Fat metabolism, so among the four major macromolecules, like carbohydrates, protein, cholanic acid, and finally, fat, I mean, lipids. In particular, in the context of bioenergetics, fat metabolism is very, very important, like carbohydrate metabolism. In the very beginning, the first session, we are going to have an overview of adipose tissue. And we will get into the biochemical structures and properties of fat molecules. The remaining three sessions, we'll take care of how fats can be digested and absorbed. And those fat molecules, I mean, fatty acid, the oxidative processes, as well as the biosynthetic pathways, will be discussed. So in the very beginning, the first session of week five is about adipose tissue. So as you can see, the accumulation of fat, in this case, abdominal fat, is obviously showing the adipose tissue. So we can just simply talk about the subcutaneous fat and the visceral fat. And those are accumulated under the skin or around the internal organs. So adipose tissue is basically filled with mostly adipocyte. Adipocyte means fat cells, simply speaking. Or the other word, the fat-storing differentiated cells. And in addition to adipocyte, inside the adipose tissue, there are other types of cells available. In particular, premature adipocyte or some fibroblast or inflammation-related inflammatory cells, like macrophages. Or a blood vessel, endothelial cells. And those are collectively stromal vascular fraction. So what's the main function of adipose tissue? So apparently, the primary function of adipose tissue is to store lipids, I mean, fats, for what? So under the energy deficient condition, those accumulated and stored lipids and fats will be utilized to drive energy production. In addition, adipose tissue can be used to protect, like a physical stress. Adipocyte, based on this diagram, so on your left. This is just a cartoon on your right. It's a real histology of white adipose tissue. As you can see, adipocyte, Is basically heavily filled with the lipids droplets. So mostly, this white stuff is the lipid droplets inside the cell. And only a few areas of each adipocyte, Includes nucleus and other organelles. So basically, fat droplets heavily developed inside the cell. And in this bottom, those red stainings indicate fats. This is very specialized staining technology technique for visualize accumulated fats. Well, as you just saw from the previous slide, adipose tissue is the main site for storing fats. So in addition to its fat storing function, adipocyte can be understood right now as endocrine organ. That means adipocyte can secrete signalling factors. And those bioactive peptides produced from adipocyte is so-called adipokine. So there are many examples of adipokines identified. So one example is leptin, leptin is obviously very, very important. Feeding suppressive hormone from adipocyte. Other than that, adiponectin, resistin, and inflammatory cytokines and TNF alpha, IL-6 indeed are synthesized and secreted from adipocyte. I'm going to give you more in-depth knowledge about adipocyte and adipose tissues. So there are two categories, white adipose tissue, WAT, or brown adipose tissue, called BAT. So subcutaneous fats or abdominal fats, and those fats, or so called, The fat molecules deposited in white adipose tissue, so energy storage purposes. But in the case of brown adipose tissue, BAT is more specialized in terms of generating heat. So let's talk more about the brown fat. So brown fats are highly developed in newborn babies or hibernating animals. And in the case of newborn human babies, the BATs make up, like, 5% of the total body mass. And it can be found from the back or along the upper half of the spine structure, more around the shoulder. Or even adults, human adults, the BAT can be identified. So main function of BAT is very, very unique. In terms of this tissue can generate heat by biochemically uncoupling the oxidative phosphorylation biochemical machinery inside the mitochondria. So what does that mean, the uncoupling? Before we get into the uncoupling of biochemical processes in BAT, I'm going to show the histology of BAT and WAT, WAT versus BAT. So as you can see, these anatomical images. So compared to very white adipose tissue, that white comes from large lipid droplets, fat droplets, inside the white adipose cell. Well, compared to white adipose tissue, those lipid droplets is quite small. But instead, the numbers are, as you can see, large lipid droplets over here. But those lipid droplets, the number and size are definitely smaller in brown adipose cells compared to white adipose cells. And then there are many, many mitochondria, Can be found in brown adipose cells. And that's why these BAT exhibit the brown color, because of too many mitochondria. So brown adipose cells, brown adipocyte in BAT tissues can generate heat throughout non-shivering thermogenesis. This is biochemical uncoupling processes. As you can remember from the core step of ATP production in carbohydrate breakdown processes. The oxidative phosphorylations throughout this electron transport chain, which is accumulated proton gradient in intermembrane mitochondrial space, can drive the production of ATP. This is typical oxidative phosphorylation processes, but the mitochondria in brown adipose cells, They express uncoupling protein membrane factors. And these proteins, it's obviously kind of a proton channel. But instead of generating ATP, that proton gradient can be dissipated to drive heat production without generating ATP. So we see this process as the uncoupling, because when proton gradients are reduced throughout those membrane structure. In particular, UCP proteins, highly developed in BAT, brown adipose tissues, can drive the heat generation instead of ATP synthesis. This is the secret of heat generation in brown adipose cells.