Thread by @nick_krontiris

In this one, mice fed an obesogenic high starch diet, although exhibited hyperglycemia and hyperinsulinemia, remained glucose tolerant and insulin sensitive despite having excess adipose tissue, in contrast to mice fed an obesogenic high-fat diet.

This is a pretty cool study delving further into the connection between ceramides, de novo lipogenesis and liver, muscle fat infiltration, the relationship between body fat content and insulin action and the effects of dietary manipulation in these factors.

- The current study reports on a dietary intervention that produces significant obesity but maintains normal insulin action in mice providing some mechanistic understanding of the phenomenon of obesity with preserved insulin sensitivity.

- Mice fed an obesogenic high starch diet diet were found to have a similar (but not identical) glucose tolerance and insulin sensitivity compared to lean chow controls, even though they accumulated the same amount of fat mass as mice fed a high fat diet.

However, there were differences in basal insulinemia and insulin response during the glucose tolerance tests that indicate that there were metabolic differences between the lean chow controls. and the mice fed the obesogenic high starch diet.

- Absolute mass, adipocyte size (i.e. cross-sectional area) and adipose tissue depot insulin sensitivity were similar between mice fed an obesogenic, high-starch diet and an obesogenic, high-fat diet.

- Therefore, these results suggest that adipocytes are unlikely to mediate the maintenance of whole body sensitivity in an obesogenic, high-starch diet.

- Both liver and muscle of mice fed an obesogenic, high-starch diet had equivalent amounts of triglyceride storage as observed in mice fed an obesogenic, high-fat diet.

- Therefore, differences in ectopic triglyceride levels in liver and muscle cannot explain the divergent insulin action in an obesogenic, high-starch diet and an obesogenic, high-fat diet.

Here comes the controversy:

- "Further investigations into the source of the greater fat deposition in Hi-ST and Hi-F mice showed that Hi-ST animals had an increased rate of de novo lipogenesis (DNL) in liver and increased levels of enzymes involved in the DNL pathway...

"...while in the Hi-F group, levels of these enzymes were decreased compared to chow and Hi-ST fed mice...

"...This suggests that upregulation of pathways converting carbohydrate to lipid could underpin the ability of Hi-ST mice to clear glucose and maintain insulin sensitivity...

"...This data indicates that synthesising fat for storage from dietary carbohydrate is less detrimental to insulin action and glucose homeostasis than metabolising and storing fat from the diet...

"...It seems mechanistically plausible that an animal consuming mainly carbohydrate would maintain or increase capacity for utilising this nutrient even if the end result is storage of triglyceride...

"..while an animal consuming mainly fat would increase capacity for utilising fat and down-regulate carbohydrate metabolic pathways."

- Also, differences in lipid species were detected between the mice fed the obesogenic, high-starch diet and the ones fed the obesogenic, high-fat diet, particularly in ceramides, that have been shown previously to correlate with insulin sensitivity/resistance.

- Results showed a negative correlation between skeletal muscle insulin sensitivity (insulin-stimulated glucose uptake) and muscle Cer18:0 levels, but it was increased in the both the high-fat and the high-starch groups to a similar extent.

- "Taken together, our data suggests that increased Cer18:0 is more closely linked to the development of (Hi-F) skeletal muscle insulin resistance."

- In the liver, DAGs were increased in both the obesogenic, high-starch diet and the obesogenic, high-fat diet to a similar degree, but ceramide species were different, particularly Cer22:0, which was one of the most abundant species.

- This particular species was increased in the mice fed the obesogenic, high-fat diet animals and was increased to a lesser extent in the fed the obesogenic, high-starch diet.

- Cer22:0 was also negatively correlated with liver insulin action, indicating that it may be involved in the development of insulin resistance.

- "Together, this data suggests that a proportion of insulin action is adaptive and may be modulated by changing the diet over a relatively short period...

"...This mechanism would enable organisms to conserve glucose for tissues unable to utilise fatty acids, such as the brain and central nervous system, during periods of carbohydrate scarcity."

TL;DR:

a) mice fed an obesogenic high starch diet, although exhibited hyperglycemia and hyperinsulinemia, remained glucose tolerant and insulin sensitive despite having excess adipose tissue, in contrast to mice fed an obesogenic high-fat diet.

b) Results suggested that specific ceramide species, such as Cer18:0 in skeletal muscle and Cer22:0 in liver may be particularily deleterious in the development of insulin resistance...

...especially during an obesogenic-high fat diet, but not as much during an obesogenic high-starch diet.

c) Based on the findings, the authors also suggest that the discrepancies between dietary interventions that produce significant obesity but maintain normal insulin action...

...is at least partly due to an increased rate of de novo lipogenesis (DNL) in liver and increased levels of enzymes involved in the DNL pathway, as they suggest that...

...synthesising fat for storage from dietary carbohydrate is less detrimental to insulin action and glucose homeostasis than metabolising and storing fat from the diet.

Insulin sensitivity is preserved in mice made obese by feeding a high starch diet (open access)

doi.org/10.7554/eLife.…

#nutrition #diet #MetabolicSyndrome #Obesity #InsulinResistance #NAFLD #Cholesterol #Triglycerides #Diabetes