Pigs were chosen deliberately. As a biomedical model, swine share striking anatomical and metabolic similarities with humans, particularly in cardiovascular physiology, body fat distribution, and digestive function. Human diet studies are notoriously difficult to control, because participants cheat, under-report, and vary wildly in adherence. Fifteen post-pubertal, non-pregnant, non-lactating gilts, Landrace by Yorkshire crosses averaging around 170 kilograms, were individually penned and paired by weight before being randomly assigned to one of two diets. Seven animals received a conventional, nutrient-balanced maintenance ration built around corn, while eight received a low-carbohydrate, high-fat formulation in which beef tallow supplied the energy normally delivered by grain. Soybean hulls were added to the high-fat diet to match the physical consistency of the control ration, and both diets were formulated to meet National Research Council requirements for swine of this age, sex, and reproductive stage.

The laboratory analysis confirmed the diets differed dramatically. The control diet contained roughly 3.3 percent crude fat and nearly 69 percent non-fiber carbohydrate on a dry matter basis, while the experimental diet contained 22.5 percent crude fat and only about 15.6 percent non-fiber carbohydrate, with neutral detergent fiber soaring to more than 44 percent thanks to the soy hulls. Interestingly, the calculated gross energy of the two rations diverged: the control diet provided approximately 3,993 kilocalories per kilogram, while the high-fat formulation came in at 3,448 kilocalories per kilogram, a discrepancy the authors attribute largely to the indigestible fiber fraction used to dilute the diet. Both rations were fed daily at 1.75 percent of each animal’s body weight, and feed refusals were weighed to calculate actual intake.

The results on body composition were the study’s most eye-catching finding. Control gilts gained weight steadily across the trial, ending roughly seven percent heavier than they started, while the high-fat group maintained a nearly constant body weight throughout. More striking was what happened beneath the skin. Measured by ultrasound adjacent the tenth thoracic vertebra, subcutaneous fat depth fell by 17.7 percent in the high-fat animals over 32 days, while control animals showed a 14 percent increase. At slaughter, the differences inside the body were even more dramatic: control gilts carried 1.74 times more visceral fat, the metabolically dangerous internal belly fat, than their high-fat counterparts, 2,660 grams versus 1,440 grams on average. Crucially, the high-fat animals did not waste away; they simply stopped depositing fat while presumably continuing to build lean tissue, an outcome the researchers interpret as a favorable shift in the ratio of muscle to fat.

Appetite appears to have played a central role. Although both groups were offered the same amount of feed relative to body weight, the high-fat gilts consumed significantly less, averaging 2.36 kilograms per day between days 19 and 32 compared with 3.09 kilograms in the control group. Calculated energy intake told the same story, with the control animals consuming more than 12,300 kilocalories daily against roughly 8,150 for the high-fat group. The authors suggest the animals reached satiety sooner and stopped eating, consistent with human trials reporting appetite suppression on ketogenic diets. They also caution, however, that the enormous soy hull load in the experimental diet may have contributed to early fullness or restricted digestible energy, a confound that future work should disentangle by examining fiber and fat effects on total tract digestibility directly.

Blood chemistry offered reassurance on one of the diet’s most feared risks: acidosis. Blood pH did not differ between treatments, and fasted values for sodium, bicarbonate, and carbon dioxide remained within normal reference ranges, indicating that four weeks on the high-fat regimen did not disrupt acid-base homeostasis. Urine ketone testing revealed that nutritional ketosis was largely absent, with no detectable ketones in the third week and only trace amounts, about 5 milligrams per deciliter, in three animals during the fourth. Yet the body composition changes occurred anyway, suggesting a metabolic shift away from fat storage that operated independently of measurable ketosis. One unexpected trend did emerge: fasting glucose in the high-fat group crept upward over the trial, ending significantly higher than controls at day 32, a pattern the authors tentatively link to early keto-adaptation and the liver’s efforts to protect glycogen reserves when adequate dietary protein fuels gluconeogenesis.

The microscopic analysis of the pancreas produced perhaps the most provocative data. Using immunofluorescent staining for insulin on formalin-fixed tissue sections, the researchers found that the percentage of active beta cells in the high-fat group was 2.81 times greater than in controls, 90.7 percent versus 42.4 percent, and that the area occupied by beta cells within the pancreatic islets was 1.81 times larger. Islet area as a percentage of total pancreatic tissue was also more than doubled. These findings suggest an enhancement of pancreatic architecture and insulin-producing capacity, which stands in contrast to earlier rodent studies reporting that long-term ketogenic diets can shrink beta-cell mass and impair glucose tolerance. The discrepancy may reflect species differences, the short feeding duration, or the moderate degree of ketosis actually achieved.

In skeletal muscle, the story was more selective. The researchers quantified insulin receptor presence by measuring the relative fluorescence intensity of antibody-labeled receptor proteins in cross-sections of the longissimus thoracis, the semimembranosus, and the kidney. Only the semimembranosus, a powerful muscle of locomotion in the hind limb, showed a statistically significant increase in insulin receptor density in the high-fed animals, with relative intensity of 32.8 versus 21.7 in controls. The longissimus showed a numerical but non-significant rise, and the kidney showed no difference. The authors propose that upregulated insulin receptors on muscle fibers may contribute to a muscle-sparing effect, supporting the anabolic influence of insulin on myofibrillar protein synthesis while ketone bodies spare amino acids from being diverted into gluconeogenesis. Notably, proximate analysis found no difference in crude fat content of the liver or longissimus muscle between groups, and although the high-fat animals had heavier livers relative to body weight, there was no biochemical indication of early fatty liver disease.

The researchers are candid about their limitations. The trial used only one sex, mature females, because intact males were unavailable and castrated males are considered irrelevant to human medicine, restricting generalizations to women. The ex vivo tissue analyses relied on just three biological replicates per group, and the 32-day feeding period is short by dietary-intervention standards; some human evidence suggests full metabolic benefits of ketogenic adherence may require twelve weeks or more. Statistical tendencies, including the glucose trajectory and the energy balance calculation, should be viewed with caution given the small sample size. Still, the authors argue the data provide preliminary justification for pursuing the metabolic impact of low-carbohydrate, high-fat diets on obesity using swine as a model, particularly the observation that animals lost fat mass without losing body weight.

For the millions of people experimenting with ketogenic eating, the study offers a cautiously encouraging signal wrapped in important caveats. In a tightly controlled animal model, replacing carbohydrate energy with animal fat reduced the most harmful fat depots, preserved body weight, enhanced markers of pancreatic insulin-producing capacity, and increased insulin receptor expression in a major locomotor muscle, all without measurable ketosis and without disturbing blood chemistry. Whether the same remodeling occurs in humans over months and years, and whether the fiber dilution that accompanied the high-fat ration contributed to the appetite effects, remains to be determined. What the pig study demonstrates is that the diet’s effects on body composition and insulin biology are real, measurable at the tissue level, and more nuanced than the popular narrative of ketosis alone would suggest.

Subject of Research: Effects of a low-carbohydrate, high-fat diet on muscle insulin receptor concentration and body composition in a swine biomedical model

Article Title: Does a low‐carb, high‐fat diet change muscle insulin receptor concentration and body composition in a swine biomedical model?

Article References: Acosta‐Castellanos, N., Tiede, S., Byrd, C. J., Borowicz, P., Young, J. M., & Berg, E. P. (2026). Does a low‐carb, high‐fat diet change muscle insulin receptor concentration and body composition in a swine biomedical model?. Physiological Reports, 14(19), Article e71124. https://doi.org/10.14814/phy2.71124

Image Credits: AI Generated

DOI: 10.14814/phy2.71124

Keywords: ketogenic diet, low-carbohydrate high-fat diet, insulin receptor, body composition, swine model, pancreatic beta cells, visceral fat, beef tallow, nutritional ketosis, skeletal muscle, metabolism, Physiological Reports