035: The Biochemistry of Why Insulin Doesn’t Make You Fat
035: The Biochemistry of Why Insulin Doesn’t Make You Fat
Mastering Nutrition Episode 35
Introduction
Do carbs and insulin make you fat? The argument centers on the ability of insulin to promote the conversion of carbohydrate to fat and lock fat in adipose tissue, as well as the necessity of glucose to provide the backbone to fat molecules within adipose tissue. But the argument ignores that all of these pathways are fundamentally regulated at a biochemical level by how much energy you need and how much you have. In episode 44 of Mastering Nutrition, we take a deep dive into the details of the biochemistry and physiology and see how insulin serves as a gauge of whole-body energy and glucose availability but simply can’t be the thing that makes you fat.
Show Notes
Do carbs and insulin make you fat? The argument centers on the ability of insulin to promote the conversion of carbohydrate to fat and lock fat in adipose tissue, as well as the necessity of glucose to provide the backbone to fat molecules within adipose tissue. But the argument ignores that all of these pathways are fundamentally regulated at a biochemical level by how much energy you need and how much you have. In episode 44 of Mastering Nutrition, we take a deep dive into the details of the biochemistry and physiology and see how insulin serves as a gauge of whole-body energy and glucose availability but simply can’t be the thing that makes you fat.
In this episode, you’ll find all of the following and more:
0:00:45 Cliff Notes
0:03:19 The biochemistry and physiology of the carbohydrate/insulin hypothesis of obesity: insulin stimulates de novo lipogenesis (fatty acid synthesis), promoting the conversion of carbohydrate to fat; insulin stimulates lipoprotein lipase (LPL) and inhibits hormone-sensitive lipase (HSL) at adipose tissue, locking fat into fat cells; since adipose tissue lacks glycerol kinase, it cannot reuse the glycerol backbone of fats digested by lipoprotein lipase, and dietary carbohydrate is needed to provide the glycerol 3-phosphate that forms the backbone of newly resynthesized triglycerides.
0:09:37 All biochemical pathways are regulated by cellular energy status. Key players are ATP, ADP, AMP, AMP kinase (AMPK), NADH/NAD+, FADH2/FAD, Ca2+, CoA and acyl CoAs, and citrate.
0:23:46 Although insulin promotes storage of fat in fat tissue, this can be overridden by low energy status.
0:33:13 Although insulin promotes fat storage, it causes a proportionate increase glucose oxidation, so no net change in caloric balance.
0:39:11 Glucose oxidation in muscle is driven by energy status and that determines the availability of glucose to adipose tissue.
0:53:51 Glucose can act as the source of glycerol 3-P for adipose tissue triglyceride synthesis, but it isn’t necessary because of gluconeogenesis and glyceroneogenesis. Furthermore, while it can serve this role, the degree to which it does so is driven by energy status.
0:58:53 Glucose can act as a source of glycerol 3-P for adipose, but it needs a source of fatty acids, which come mainly from fat as long as energy status is high enough.
0:59:54 Insulin can drive de novo lipogenesis, but only when energy status is high enough.
1:13:07 What happens when we eat carbs alone, fat alone, or both in the context of low and high energy status.
1:25:20 The path to weight loss is the path to a sustainable caloric deficit.
Masterclass Lessons Related to “The Biochemistry of Why Insulin Doesn’t Make You Fat”
What Shuts Down Glycolysis and Glucose Uptake? Too Much Energy. | MWM 2.21
What Shuts Down Fat Burning? Too Much Energy. | MWM 2.22
Other Podcast Episodes and Posts Related to “The Biochemistry of Why Insulin Doesn’t Make You Fat”
Ketogenesis Isn’t All About Carbs and Insulin | Mastering Nutrition Episode 17
Insulin Resistance Isn’t All About Carbs and Insulin | Mastering Nutrition Episode 20
Is Insulin Resistance Really Making Us Fat? | November 2010 blog post
Research and Educational Resources Related to “The Biochemistry of Why Insulin Doesn’t Make You Fat”
For biochemistry textbooks, I recommend Ferrier, Biochemistry for beginners and Berg, Biochemistry and for intermediate or advanced readers. The Berg book is in its eighth edition (2015), but the fifth edition (2002) is freely available. Huge swaths are the same between them, but many portions are updated and a handful of sections are added new or fundamentally changed. The free version is hard to read straight through because it is searchable but not browsable. The Kindle or hardcover versions are much easier to read.
Tortora, Principles of Anatomy and Physiology: 14th Edition, 2013 is a good resource for understanding the transport routes of fat and carbohydrate from an anatomy and physiology perspective.
Byers et al. Avian and Mammalian Facilitative Glucose Transporters. 2017.
Kersten. Physiological regulation of lipoprotein lipase. 2014.
Winder. Cellular energy sensing and signaling by AMP-activated protein kinase. 2007.
Mitrou et al. Rates of Glucose Uptake in Adipose Tissue and Muscle in Vivo after a Mixed Meal in Women with Morbid Obesity. 2009.
Reshef. Glyceroneogenesis and the triglyceride/fatty acid cycle. 2003.
Hanson. Glyceroneogenesis revisited. 2003.
Hellerstein. De novo lipogenesis in humans: metabolic and regulatory aspects. 1999.
Acheson. Glycogen storage capacity and de novo lipogenesis during massive carbohydrate overfeeding in man. 1988.
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