Early exposure to fat-related food smells increases lifelong obesity risk

By Dr. Priyom Bose, Ph.D.Reviewed by Benedette Cuffari, M.Sc.Dec 7 2025

New experimental evidence shows that food smells encountered before birth and during early life can rewire brain and metabolic responses to fat, increasing the risk of obesity later in life, even in the absence of maternal obesity or excess calories.

Study: Fat sensory cues in early life program central response to food and obesity. Image Credit: Shadows Leader / Shutterstock.com

A recent study published in the journal Nature Metabolism investigates how fat-related sensory cues during the early developmental period influence the regulation of central responses to food cues, metabolic health, and obesity in adulthood.

The effect of maternal obesity on children

Developmental exposure to a maternal diet high in calories and fat is a significant risk factor for lifelong obesity and metabolic disorders. Several studies have confirmed the metabolic consequences of maternal high-fat diet (HFD) consumption, some of which include excess gestational weight gain, insulin resistance, and adiposity.

Despite strong correlations observed between maternal obesity or nutritional components of HFD and the risk of obesity development in offspring, additional research is needed to identify other specific factors of HFD that induce metabolic programming.

In addition to nutrients, food also contains non-nutritive sensory components, such as volatile odors. Throughout development, fetuses and newborns are exposed to both nutritive and non-nutritive sensory signals from food.

Perinatal olfactory experiences form sensory memories that contribute to food preferences and eating habits into adulthood. Thus, it is crucial to understand how non-nutritive sensory cues from HFD during development lead to long term effects, particularly on dietary preference, intake, and metabolic responses, is crucial.

About the study

The researchers of the current study developed an isonutritional diet using a normal chow diet (NCD) flavored with fat-related odors. This diet was used to separate nutritive caloric components from non-nutritive sensory components of HFD.

NCD was enriched with bacon odors to create an isonutritional bacon-flavored diet (BFD). Notably, BFD mimics the commonly used lard-based HFD (HFD_lard). A butter fat-based HFD (HFD_butter) was also developed for a non-pork-based HFD.

Study findings

A complex odor profile of the diets was identified, comprising 155 volatile compounds, primarily aldehydes, ketones, and alcohols. Hierarchical cluster analysis revealed that, although HFD and HFD_lard shared high sensory similarity, their volatile profiles differed from those of HFD_butter and NCD. Further analysis indicated that the sensory profile of BFD is similar to that of HFD_lard, while its nutritional profile resembles that of NCD.

Experimental analysis confirmed that food odors induce phosphorylation of S6 in olfactory sensory neurons (OSNs) residing in the main olfactory epithelium. BFD was found to exhibit greater subjective olfactory similarity to HFD_lard than NCD.

The researchers also developed a mouse model of developmental exposure to fat-related sensory cues that is independent of maternal insulin resistance, adiposity, weight gain, and changes in maternal lipid components.

Early-life exposure to fat-related sensory cues leads to metabolic defects in adulthood

Control mice exposed to NCD but naive to HFD_lard during development (NCD_dev) did not exhibit any changes in interscapular brown adipose tissue (iBAT) temperature or in hepatic mechanistic target of rapamycin (mTOR) phosphorylation (p-mTOR) responses. However, iBAT temperature and hepatic p-mTOR increased upon HFD_lard odor exposure in mice developmentally exposed to BFD (BFD_dev) but naive to HFD_lard.

The heightened obesogenic responses observed in BFD_dev animals were triggered explicitly by developmental exposure to BFD, suggesting that early life is a critical time of vulnerability for metabolic programming by fat-related sensory cues. Notably, exposure to these cues during development alone could be sufficient to worsen HFD_lard-induced obesity, regardless of maternal obesity or insulin resistance.

Lactation may represent the period of greatest sensitivity to fat sensory cues in females. In contrast, males require exposure to BFD throughout the entire developmental period to exhibit heightened responses to HFD_lard.

Eight-week-old BFD_dev and control NCD_dev animals were exposed to HFD_butter to determine whether metabolic responses were specific to the pork-based HFD, which closely resembles BFD in its sensory properties. To this end, early exposure to fat sensory cues, such as those mimicking HFD_lard, increases susceptibility to obesity, even when animals are then challenged with other types of high-fat diets, suggesting that sensory-driven metabolic programming can generalize to a range of hypercaloric diets.

Fat-related sensory cues can affect metabolism, influencing how the body responds to different diets. Although the exact match in sensory cues between early-life and adult obesogenic diets was not required for metabolic effects, some degree of sensory similarity may play a significant role in this association.

BFD feeding altered the volatile profile of both amniotic fluid and milk, which subsequently changes the sensory food experiences of offspring during both the in utero and neonatal periods.

Moreover, iBAT thermogenesis was reduced in BFD_dev compared with NCD_dev, accompanied by lower expression of thermogenic-related genes in iBAT, including Cidea and Pparg. These findings indicate that developmental exposure to HFD-related sensory cues impairs metabolic flexibility and homeostatic responses to HFD in adult mice.

Developmental exposure to fat-related sensory cues caused a specific impairment in Agouti-related peptide (AgRP) neuronal responses to dietary fat. However, responses to key hormonal signals were unaffected.